Antiviral Treatment Of Chronic Hepatitis Research Articles

Metabolic effects and cardiovascular disease risks of antiviral treatments in patients with chronic hepatitis B

AbstractDifferent antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)‐induced dyslipidemia and its associated outcomes are significant. This study utilized 15‐year historical cohort including patients with CHB in Korea and consisted of two parts: the single‐antiviral and switch‐antiviral cohorts. In the single‐antiviral cohort, patients were divided into four groups (entecavir [ETV]‐only, tenofovir disoproxil fumarate [TDF]‐only, TAF‐only, and non‐antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch‐antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single‐antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well‐balanced after PSM. Changes in total cholesterol were significantly different between groups (−2.57 mg/dL/year in the TDF‐only group and +2.88 mg/dL/year in the TAF‐only group; p = 0.002 and p = 0.02, respectively). In the TDF‐only group, HDL cholesterol decreased as well (−0.55 mg/dL/year; p < 0.001). The TAF‐only group had the greatest increase in ASCVD risk, followed by the TDF‐only group and the non‐antiviral group. In the switch‐antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (−1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (−2.96 mg/dL/year in the TDF‐only group and +3.09 mg/dL/year in the TAF‐only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin‐treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.

New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.

The efficacy of antiviral treatment in chronic hepatitis B patients with hepatic steatosis

Background & aimsWith a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. MethodsCHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. ResultsIn total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245–0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. ConclusionsAmong CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide

Background & AimsBulevirtide is a first-in-class entry inhibitor antiviral treatment for chronic hepatitis D. The viral kinetics during bulevirtide therapy and the effect of combining bulevirtide with pegylated-interferon (Peg-IFN) are unknown. MethodsWe used mathematical modelling to analyze the viral kinetics in two French observational cohorts of 183 patients receiving bulevirtide with or without Peg-IFN for 48 weeks. ResultsThe efficacy of bulevirtide in blocking cell infection was estimated to 90.3%, whereas Peg-IFN blocked viral production with an efficacy of 92.4%, albeit with large inter-individual variabilities. The addition of Peg-IFN to bulevirtide was associated with a more rapid virological decline, with a rate of virological response (>2 log of decline or undetectability) at week 48 of 86.9% (95% prediction interval [PI] = [79.7–95.0]), compared with 56.1% (95% PI = [46.4–66.7]) with bulevirtide only. The model was also used to predict the probability to achieve a cure of viral infection, with a rate of 8.8% (95% PI = [3.5–13.2]) with bulevirtide compared with 18.8% (95% PI = [11.6–29.0]) with bulevirtide + Peg-IFN. Mathematical modelling suggests that after 144 weeks of treatment, the rates of viral cure could be 42.1% (95% PI = [33.3–52.6]) with bulevirtide and 66.7% (95% PI = [56.5–76.8]) with bulevirtide + Peg-IFN. ConclusionsIn this analysis of real-world data, Peg-IFN strongly enhanced the kinetics of viral decline in patients treated with bulevirtide. Randomized clinical trials are warranted to assess the virological and clinical benefit of this combination, and to identify predictors of poor response to treatment. Impact and implicationsBulevirtide has been approved for chronic HDV infection by regulatory agencies in Europe based on its good safety profile and rapid virological response after treatment initiation, but the optimal duration of treatment and the chance to achieve a sustained virological response remain unknown. The results presented in this study have a high impact for clinicians and investigators as they provide important knowledge on the long-term virological benefits of a combination of Peg-IFN and bulevirtide in patients with CHD. Clinical trials are now warranted to confirm those predictions.

A cross-sectional survey on the types of antiviral treatment plans for patients with chronic hepatitis B

Objective: To understand the current antiviral treatment status and various clinical types of treatment plans in Xiamen City so as to explore ways to improve and optimize the diagnosis and treatment standards for chronic hepatitis B. Methods: A cross-sectional survey method was used to study the antiviral treatment status and treatment plans for chronic hepatitis B patients who visited and were diagnosed in the Department of Infectious Diseases and Hepatology of all tertiary hospitals in Xiamen City at 0:00~23:59 on May 25, 2022. Results: A total of 665 cases were surveyed in this study, with an antiviral treatment rate of 81.2%(540/665). The antiviral treatment rate of patients who accorded with the current guidelines for antiviral treatment indications was 85.8%(507/591). The antiviral treatment rate for 362 outpatients was 72.9%(264/362). Among them, the antiviral treatment rates were 80.1%, 89.3%, and 25.0%(226/282, 25/28, 13/52), respectively, for patients diagnosed with chronic hepatitis B, hepatitis B cirrhosis, and hepatitis B surface antigen-carrying status. The treatment plan for all outpatient patients was mainly oral nucleos(t)ide analogues, accounting for 59.1%(214/362). The antiviral treatment rate for 303 inpatients was 91.1%(276/303). The various clinical types of antiviral therapy rates among all patients were 70%~95%. The antiviral treatment plan for inpatients was mainly based on pegylated interferon alpha treatment, accounting for 72.6%(220/303). Conclusion: Antiviral treatment for chronic hepatitis B in Xiamen City can still be strengthened to meet the current demand for expanding antiviral treatment indications. Antiviral treatment rates and various types of treatment plans differ between outpatients and inpatients; thus, further awareness and acceptance of the goal of improving antiviral therapy, especially in outpatients, and the possibility for a clinical cure based on pegylated interferon alpha treatment are needed to maximize the benefit to more patients.

Metabolomic analysis identifies dysregulation of lipid metabolism in the immune clearance phase of chronic hepatitis B patients

There is an accelerated progression of liver necroinflammation and fibrosis in the liver during the immune clearance (IC) phase of Chronic hepatitis B virus (HBV) infection, which are critical indicators of antiviral treatment for chronic hepatitis B (CHB) infection. This study applied serum metabolomics to identify the potential metabolite biomarkers for differential diagnosis between the CHB immune tolerance (IT) and Immune clearance (IC) phases. A liquid chromatography-mass spectrometry (LC-MS)-based approach was applied to evaluate and compared the serum metabolic profiles of 28 patients in IT phase and 33 patients in IC phase and appropriate statistical methods with MetaboAnalystR 2.0 R package to analyze those metabolites. The differential metabolites between IT and TC groups were classified and the top altered classification were lipids and lipid-like molecules and fatty acyls, clearly indicating that there were differences in the lipid metabolomic profile of HBV-infected patients with IT vs. IR phase. We identified the top 10 potential metabolite biomarkers for differential diagnosis between IT and IR. There were four lipid metabolites among them and the AUC of two of them, octadecadienoyl-sn-glycero-3-phosphocholine and 3-Cycloheptene-l-acetic acid, were 0.983 and 0.933. octadecadienoyl-sn-glycero-3-phosphocholine is Diacylglycerol (18:2n6/18:0) and 3-Cycloheptene-l-acetic acid is hydroxy fatty acids, both of which were associated with lipid metabolism. This study not only provides the potential metabolic biomarkers but also insight into the mechanism of CHB progression during IT clearance phase.

A novel hepatitis B virus capsid assembly modulator QL-007 inhibits HBV replication and infection through altering capsid assembly

The core protein allosteric modulators (CpAMs) have shown great potential as highly effective antiviral drugs against hepatitis B virus (HBV) in preclinical studies and clinical trials. In this study, we evaluated a small molecule compound called QL-007, which could potentially influence capsid assembly, using HBV replicated and susceptible cell models as well as mice infected with rAAV-HBV. QL-007 significantly inhibited HBV replication in a dose-dependent manner both in vitro and in vivo, resulting in significant decreases in HBV DNA, 3.5 kb HBV RNA and HBeAg. Furthermore, QL-007 not only induced the formation of misshaped Cp149 capsids but also possessed the capability to disassemble HBV capsids. It is noteworthy that QL-007 effectively reduced cccDNA biosynthesis in de novo infections. Mechanistically, QL-007 blocked the encapsidation of pgRNA and induced aberrant polymers assembly at concentrations ≥100 nM, while having no impact on the stability of core proteins. In conclusion, our findings underscore the potential of QL-007 as an effective agent against HBV replication and introduce it as a novel CpAM for the antiviral treatment of chronic hepatitis B.

THU-193 - The influence of direct acting antiviral treatment in chronic hepatitis C virus infection on arterial stiffness

THU-193 - The influence of direct acting antiviral treatment in chronic hepatitis C virus infection on arterial stiffness

Health-Related Quality of Life after Direct Acting Antiviral Treatment for Chronic Hepatitis C in a community Led Program

Health-Related Quality of Life after Direct Acting Antiviral Treatment for Chronic Hepatitis C in a community Led Program

AMAP Score and Its Combination With Liver Stiffness Measurement Accurately Assess Liver Fibrosis in Chronic Hepatitis B Patients

The changes in liver stiffness measurement (LSM) are unreliable to estimate regression of fibrosis during antiviral treatment for chronic hepatitis B (CHB) patients. The age-male-albumin-bilirubin-platelets score (aMAP), as an accurate hepatocellular carcinoma risk score, may reflect the liver fibrosis stage. Here, we aimed to evaluate the performance of aMAP for diagnosing liver fibrosis in CHB patients with or without treatment. A total of 2053 patients from 2 real-world cohorts and 2 multicentric randomized controlled trials in China were enrolled, among which 2053 CHB patients were included in the cross-sectional analysis, and 889 CHB patients with paired liver biopsies before and after 72 or 104 weeks of treatment were included in the longitudinal analysis. In the cross-sectional analysis, the areas under the receiver operating characteristic curve of aMAP in diagnosing cirrhosis and advanced fibrosis were 0.788 and 0.757, which were comparable with or significantly higher than those of the fibrosis index based on 4 factors and the aspartate aminotransferase-platelet ratio. The stepwise approach using aMAP and LSM further improved performance in detecting cirrhosis and advanced fibrosis with the smallest uncertainty area (29.7% and 46.2%, respectively) and high accuracy (82.3% and 79.8%, respectively). In the longitudinal analysis, we established a novel model (aMAP-LSM model) by calculating aMAP and LSM results before and after treatment, which had satisfactory performance in diagnosing cirrhosis and advanced fibrosis after treatment (area under the receiver operating characteristic curve, 0.839 and 0.840, respectively), especially for those with a significant decrease in LSM after treatment (vs LSM alone, 0.828 vs 0.748; P < .001 [cirrhosis]; 0.825 vs 0.750; P < .001 [advanced fibrosis]). The aMAP score is a promising noninvasive tool for diagnosing fibrosis in CHB patients. The aMAP-LSM model could accurately estimate fibrosis stage for treated CHB patients.

Cost-effectiveness of expanded antiviral treatment for chronic hepatitis B virus infection in China: an economic evaluation

China, which has the largest chronic hepatitis B virus (HBV) burden, may expand antiviral therapy to attain the World Health Organization (WHO)-2030 goal of 65% reduction in mortality. We evaluated health outcomes and cost-effectiveness of chronic HBV infection treatments based on alanine transaminase (ALT) antiviral treatment initiation thresholds and coverage in China to identify an optimal strategy. A decision-tree Markov state-transition model evaluated the cost-effectiveness of expanded antiviral treatment for chronic HBV infection by simulating 136 scenarios by ALT treatment initiation thresholds (40 U/L, 35 U/L for males and 25 U/L for females, 30 U/L for males and 19 U/L for females, and treating HBsAg+individuals regardless of ALT values), population age groups (18-80, 30-80, and 40-80 years), implementation durations (2023, 2028, and 2033) under and treatment coverages (20%, 40%, 60%, and 80%). Deterministic and probabilistic sensitivity analyses explored model uncertainty. Besides the status quo, we finally simulated 135 treatment-expanding scenarios based on the cross combination of different thresholds of ALT, treatment coverages, population's age groups and implementation time. For the status quo, a cumulative incidence of 16,038-42,691 HBV-related complications and 3116-18,428 related deaths will happened between 2030 and 2050. When the treatment threshold is expanded to 'ALT > 35 in males & ALT > 25 in females' immediately without expanding treatment coverage, it will save 2554 HBV-related complications and 348 related deaths compared to the status quo among the whole cohort by 2030, and US$ 156 million more will be costed for gaining 2962 more QALYs. If we just expand the ALT threshold to ALT > 30 in males & ALT > 19 in females, 3247 HBV-related complications and 470 related deaths will be prevented by 2030 under the current treatment coverage of 20%, which will cost US$ 242 million, US$ 583 million or US$ 606 million more by the year of 2030, 2040 or 2050, respectively. Treatment expanded to HBsAg+will save the largest number of HBV-related complications and death. This expanding strategy also results in large complications or death reduction when it is limited to patients older than 30 years or 40 years. Under this strategy, four scenarios (Treating HBsAg+ with coverage of 60% or 80% for patients older than 18 years or 30 years) showed the effectiveness in reaching the target before the year 2030. Among all the strategies, treatment expanded to HBsAg+would cost the most while providing the highest total QALYs compared to other strategies with similar implementation scenarios. ALT thresholds of 30 U/L and 19 U/L for males and females, respectively, with 80% coverage for 18-80 years, can attain the goal by2043. Treating HBsAg+individuals with 80% coverage for 18-80 years is optimal; earlier implementation of expanded antiviral treatment with a modified ALT threshold could decrease HBV-related complications and deaths to support the global target of 65% reduction in viral hepatitis B deaths. This study was funded by Global Center for Infectious Disease and Policy Research (BMU2022XY030); Global Health and Infectious Diseases Group (BMU2022XY030); The Chinese Foundations for Hepatitis Control and Prevention (2021ZC032); National Science and Technology Project on Development Assistance for Technology, Developing China-ASEAN Public Health Research and Development Collaborating Center (KY202101004); in part by National Key R&D Program of China (2022YFC2505100).

The Efficacy of Antiviral Treatment for Chronic Hepatitis B Patients with Normal ALT Levels: A Systematic Review and Meta-analysis

Context: When nucleos(t)ide analogues (NAs) were applied clinically to manage chronic hepatitis B virus infection, the prognosis of chronic hepatitis B (CHB) patients greatly improved. However, certain CHB patients with normal alanine aminotransferase (ALT) levels were not used to be considered as the population with the need for antiviral treatment. Objectives: This systematic review and meta-analysis collected and analyzed data from clinical trials to assess and compare the efficacy of antiviral treatment among patients with elevated and normal ALT levels. Methods: A systematic search was performed to gather studies published from 1990.01 to 2022.08 in PubMed and Web of Science databases. The quality of the literature was assessed, and 16 studies were included for further analysis. Basic information on included studies and study populations was collected. A meta-analysis was carried out to evaluate three major outcomes of viral response, hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion after NAs treatment based on data extracted from these studies. Odds ratios (ORs) with 95% confidence intervals (CIs) for all outcomes were calculated using fixed-effects models. Results: In the 16 relevant studies, 5,345 patients met the inclusion criteria, including 3,687 patients receiving NAs treatment. All patients were grouped into one with elevated ALT and another with normal ALT based on whether their pretreatment ALT levels &gt; 1*upper limit of normal (ULN). For patients receiving lamivudine, the viral response showed no significant difference between the groups with elevated and normal ALT levels (pooled log OR: 0.51 [-0.23 - 1.26], P = 0.79); the pooled log OR for HBeAg loss was 1.19 (0.63 - 1.76, P = 0.03) and pooled log OR for HBeAg seroconversion was 2.19 (0.91 - 3.47, P = 0.40). For patients receiving first-line therapy with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), the viral response showed no significant difference between the two groups: Pooled log OR (0.38 [-0.22 - 0.97], P = 0.10). The pooled log OR for HBeAg loss and HBeAg seroconversion was (-0.07 [-0.81 - 0.67], P = 0.68) and (0.40 [-0.84 - 1.63], P = 0.88), respectively. Conclusions: The efficacies of first-line therapy with TDF and ETV treatments were similar in groups with elevated and normal ALT levels for the outcomes of viral response and HBeAg loss. These findings may support further treatment of CHB patients with normal ALT levels.

Some HBeAg-negative chronic hepatitis B patients treated with nucleos(t)ide analogue can achieve HBsAg loss after drug withdrawal: stop-to-cure may be coming

Nucleoside/Nucleotide analogues (NAs) are widely used for the antiviral treatment of chronic hepatitis B (CHB), however, it is difficult to achieve serum hepatitis B surface antigen (HBsAg) loss with NAs therapy. In recent years, several prospective trails have reported that HBsAg loss (functional cure or clinical cure) also occurs in a small number of hepatitis B e antigen (HBeAg) negative CHB patients who discontinued long-term treatment with NAs. Accordingly, the "stop-to-cure" strategy is proposed. Although the mechanism has not been fully elucidated, the known factors related to serum HBsAg loss with NAs withdrawal include HBV genotype, duration of NAs treatment, serum HBsAg and HBV RNA levels at end-of-treatment, and ethnic differences. In the review, we discuss the best time to stop NAs therapy, the potential markers for predicting relapse after cessation of NAs and the possible mechanism of "stop-to-cure" in HBeAg-negative CHB patients, and propose some suggestions on the time of retreatment.

THU326 - Exosomal cargo as a key player of the immune response after direct-acting antiviral treatment in chronic hepatitis C patients

THU326 - Exosomal cargo as a key player of the immune response after direct-acting antiviral treatment in chronic hepatitis C patients

Hepatocellular carcinoma incidence in chronic hepatitis C patients according to sustained virological response (SVR) with interferon‐based therapies and baseline characteristics

AbstractIntroductionHepatocellular carcinoma (HCC) is the second most common cause of cancer‐related death worldwide with increasing incidence. Effective antiviral treatment for chronic hepatitis C (CHC) became available in the last 7 years but despite the WHO Hepatitis elimination targets, they are not universally available today in all regions for all the patients, indicating still a bleak outlook for CHC‐associated HCC in the next decades.AimTo assess the HCC incidence in relation to interferon (IFN)‐based antiviral treatment response and baseline characteristics of a large cohort of chronic hepatitis C (CHC) patients from a single institution.MethodsWe retrospectively collected data of CHC patients, who were diagnosed between 1989 and 2011 and treated at the AKH‐University Hospital of Vienna before the introduction of direct‐acting antiviral (DAA) only therapy. We analysed the HCC incidence in patients with a sustained virological response (SVR) and without SVR according to the patients' baseline characteristics.ResultsOur study included 2134 patients, who were treated or not treated with IFN‐based antiviral treatment and had long‐term follow‐up available. The overall HCC incidence in this cohort was 6.2% (132 HCC cases over a median follow‐up period of 9 years). According to the baseline fibrosis stage, the overall HCC incidence was: 1.1% in patients with baseline fibrosis stage F0‐2, 8.2% in F3 and 20.6% in F4 patients. The HCC incidence was significantly higher in non‐SVR and no‐treatment group as compared with SVR patients: 12.4% vs 1.9%, P &lt; .0001, 7.3% vs 1.9%, P &lt; .0001. In multivariate analysis, lower platelet count (odds ratio‐OR = ‐0.1, 95% CI: 0.15‐0.63), for the SVR group and presence of cirrhosis (OR = 3.6, 95% CI: 1.59‐8.17), ALBI grade &gt;=2 (OR = 2.3, 95% CI: 1.0‐5.3) for the non‐SVR group were independently associated with HCC occurrence. For the group of patients with no treatment, the only predictor for HCC was high baseline alpha‐fetoprotein values (OR = 10.2, 95% CI: 2.2‐47.9).ConclusionThe achievement of SVR significantly reduces the risk for HCC occurrence during long‐term follow‐up. However, the risk remains high in successfully treated patients with low platelet count and in patients who did not achieve SVR with more advanced liver disease. These risk factors should be considered in decision‐making of HCC surveillance in this settling.

Soluble inflammatory mediators identify HCV patients who may be cured with four weeks of antiviral treatment.

Soluble inflammatory mediators (SIM) can be predictive of treatment outcome in antiviral treatment of chronic hepatitis C. Recently, it was shown that a subgroup of patients can be cured with four weeks of therapy. We here profiled patients for 70 SIM before and during treatment of hepatitis C with glecaprevir/pibrentasvir (GLE/PIB) +/- ribavirin. Proximity extension assay was performed in a total of 32 patients. Pre-treatment SIM profiles did not distinguish patients achieving an SVR (n=21) from patients experiencing antiviral relapse (n=11). However, after 4weeks of therapy, eight markers were identified that could distinguish patients with SVR from the relapsed group, namely MMP-10, CCL20, CXCL11, FGF-23, TNF, MCP-2, IL-18R1 and CXCL10. Thus, this study shows that a distinct on-treatment immune profile is associated with cure of HCV infection after ultrashort treatment.

Novel machine learning models outperform risk scores in predicting hepatocellular carcinoma in patients with chronic viral hepatitis

Background & AimsAccurate hepatocellular carcinoma (HCC) risk prediction facilitates appropriate surveillance strategy and reduces cancer mortality. We aimed to derive and validate novel machine learning models to predict HCC in a territory-wide cohort of patients with chronic viral hepatitis (CVH) using data from the Hospital Authority Data Collaboration Lab (HADCL).MethodsThis was a territory-wide, retrospective, observational, cohort study of patients with CVH in Hong Kong in 2000–2018 identified from HADCL based on viral markers, diagnosis codes, and antiviral treatment for chronic hepatitis B and/or C. The cohort was randomly split into training and validation cohorts in a 7:3 ratio. Five popular machine learning methods, namely, logistic regression, ridge regression, AdaBoost, decision tree, and random forest, were performed and compared to find the best prediction model.ResultsA total of 124,006 patients with CVH with complete data were included to build the models. In the training cohort (n = 86,804; 6,821 HCC), ridge regression (area under the receiver operating characteristic curve [AUROC] 0.842), decision tree (0.952), and random forest (0.992) performed the best. In the validation cohort (n = 37,202; 2,875 HCC), ridge regression (AUROC 0.844) and random forest (0.837) maintained their accuracy, which was significantly higher than those of HCC risk scores: CU-HCC (0.672), GAG-HCC (0.745), REACH-B (0.671), PAGE-B (0.748), and REAL-B (0.712) scores. The low cut-off (0.07) of HCC ridge score (HCC-RS) achieved 90.0% sensitivity and 98.6% negative predictive value (NPV) in the validation cohort. The high cut-off (0.15) of HCC-RS achieved high specificity (90.0%) and NPV (95.6%); 31.1% of patients remained indeterminate.ConclusionsHCC-RS from the ridge regression machine learning model accurately predicted HCC in patients with CVH. These machine learning models may be developed as built-in functional keys or calculators in electronic health systems to reduce cancer mortality.Lay summaryNovel machine learning models generated accurate risk scores for hepatocellular carcinoma (HCC) in patients with chronic viral hepatitis. HCC ridge score was consistently more accurate than existing HCC risk scores. These models may be incorporated into electronic medical health systems to develop appropriate cancer surveillance strategies and reduce cancer death.

Variable Normalization of Naïve CD4+ Lymphopenia and Markers of Monocyte and T Cell Activation over the Course of Direct-Acting Anti-Viral Treatment of Chronic Hepatitis C Virus Infection.

Chronic hepatitis C virus (HCV) infection is associated with naïve CD4+ T cell lymphopenia and long-standing/persistent elevation of cellular and soluble immune activation parameters, the latter heightened in the setting of HIV co-infection. The underlying mechanisms are not completely understood. However, we recently reported that accelerated peripheral cell death may contribute to naïve CD4+ T cell loss and that mechanistic relationships between monocyte activation, T cell activation, and soluble inflammatory mediators may also contribute. Chronic HCV infection can be cured by direct-acting anti-viral (DAA) therapy, and success is defined as sustained virological response (SVR, undetectable HCV RNA (ribonucleic acid) at 12 weeks after DAA treatment completion). However, there is no general consensus on the short-term and long-term immunological outcomes of DAA therapy. Here, we consolidate previous reports on the partial normalization of naïve CD4+ lymphopenia and T cell immune activation and the apparent irreversibility of monocyte activation following DAA therapy in HCV infected and HCV/HIV co-infected individuals. Further, advanced age and cirrhosis are associated with delayed or abrogation of immune reconstitution after DAA therapy, an indication that non-viral factors also likely contribute to host immune dysregulation in HCV infection.

Laboratory monitoring and antiviral treatment for chronic hepatitis B among routine care patients in the United States.

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109moved up to 'definite' status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with 'definite' indications for antiviral therapy remained untreated.

Clinical significance and management strategies of low-level viremia during the treatment of chronic hepatitis B

Chronic hepatitis B and its related complications seriously endanger the lives and health of our country people. Although the first-line nucleos(t)ide analogs such as entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide fumarate can inhibit virus replication to a certain extent, delay or prevent disease progression, and reduce the incidence of hepatitis B-related liver cancer, but in clinical practice, HBV DNA positivity is still detected continuously or intermittently in the serum of some patients. Therefore, low-level viremia has received widespread attention and triggered discussion, and has become the difficulties and hotspot of antiviral treatment of chronic hepatitis B. This article summarizes and discusses the definition and incidence in line with the main guidelines and studies, impact of disease control and clinical prognosis, and the current treatment options in order to provide definite reference for the management of low-level viremia during antiviral therapy in patients with chronic hepatitis B.