Prediction Modelling for Gastroesophageal Variceal Bleeding in Patients With Chronic Hepatitis B Using Four-dimensional Flow MRI.

Background/Aims: In this study, we aim to develop a model for predicting gastroesophageal varices (GEV) bleeding in patients with chronic hepatitis B (CHB) by utilizing hemodynamic parameters obtained through four-dimensional flow MRI (4D flow MRI). Methods: This study conducted a prospective enrollment of CHB patients suspected of GEV from October 2021 to May 2022. The severity of varices and bleeding risk were evaluated using clinical findings and upper gastrointestinal endoscopy, and patients were classified into high-risk and non-high-risk groups. The study utilized serological examination, ultrasonographic examination, and 4D flow MRI. Relevant parameters were selected through univariate and multivariate analyses, and a prediction model was established using binary logistic regression analysis. The model was combined with the Baveno Ⅵ/Ⅶ and Expanded Baveno Ⅵ/Ⅶ criteria to evaluate diagnostic efficacy and the risk of avoiding endoscopic examination. Results: A total of 40 CHB patients were enrolled and categorized into the high-risk group (n = 15) and the non-high-risk group (n = 25). The spleen diameter and regurgitant fraction (R%) were independent predictors of variceal bleeding and a predictive model was established. The combination of this prediction model and the Baveno Ⅵ/Ⅶ criteria achieved high diagnostic efficiency, enabling 45.00% (18/40) of patients to be exempted from the unnecessary endoscopic procedure and the high-risk misclassification rate (0%) was less than 5%. Conclusion: The prediction model generated by 4D flow MRI has the potential to assess the likelihood of varices and can be supplemented by the Baveno VI/VII criteria to improve diagnostic accuracy in CHB patients.

Nucleos(t)ide analogs to treat patients with positive hepatitis B virus deoxyribonucleic acid and normal alanine transaminase: protocol for an open-label single-center randomized parallel controlled trial.

BACKGROUND: Direct high-quality evidence remains absent on the benefits of HBeAg-negative chronic hepatitis B patients (CHB) with normal alanine transaminase (ALT) and positive HBV DNA after nucleos(t)ide analogs (NAs) treatment. METHODS: This is a single-center, open-label, randomized parallel controlled trial with a follow-up duration of 96 weeks. An estimated 300 patients will be recruited at West China Hospital of Sichuan University, China. After stratified by serum HBV DNA (< 2000 vs. ≥ 2000 IU/ml), eligible patients will be randomized (allocation ratio 1:1) to receive either antiviral therapy (the treatment group) or regular examination alone (the control group). The primary outcomes are rates of virological response and changes in the levels of serum HBV pregenomic RNA (pgRNA) and scores of health-related qualities of life. DISCUSSION: This randomized controlled trial focuses on HBeAg-negative patients with normal ALT, including those of the inactive carrier phase and the grey zone, whose antiviral treatment remains controversial. Additionally, a health-related quality of life scale is introduced to comprehensively estimate the benefit of antiviral treatment apart from virological response and adverse liver events. Meaningfully, the study findings will provide high-quality and direct evidence for optimal clinical management in such populations. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300069391) on 15 March 2023.

The impact of hepatitis B surface antigen seroconversion on the durability of functional cure induced by pegylated interferon alpha treatment.

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss is regarded as a pivotal criterion for assessing functional cure in patients diagnosed chronic hepatitis B (CHB). We conducted the research to investigate the real-world performance of HBsAg seroconversion in sustaining HBsAg loss. METHODS: This retrospective analysis confirmed 295 patients who attained HBsAg loss through combination therapy involving nucleos(t)ide analogues (NAs) and pegylated interferon alpha (peg-IFNα). Employing Kaplan-Meier estimates method to conduct survival analysis. The forest plot was used to visualize the results of multivariate Cox regression, and selected variables were included in the nomogram. RESULTS: HBsAg seroreversion was observed in 45 patients during follow-up periods, with a lower recurrence risk in patients with HBsAg seroconversion at the end of peg-IFNα therapy (EOT) (10.3% vs 37.3% at 96-week, P < 0.0001). Moreover, the sustainability of hepatitis B surface antibody (anti-HBs) in participants continuing therapy after HBsAg seroconversion was superior to those discontinued prematurely (72.5% vs 54.5% at 96 weeks, P = 0.012). Additionally, the former group was also relatively less likely to experience HBsAg reversion during long-term observation (8.4% vs 14.3% at 96 weeks, P = 0.280). Hepatitis B envelope antigen (HBeAg) status, anti-HBs status and consolidation treatment screened by multivariable analysis were utilized to construct a predictive model for HBsAg reversion. The concordance index(C-index = 0.77) and calibration plots indicated satisfactory discrimination and consistency of nomogram. CONCLUSIONS: HBsAg seroconversion was beneficial for sustaining functional cure in patients treated with peg-IFNα. Continuing consolidation therapy after HBsAg seroconversion also contributed to maintain HBsAg seroconversion and improve the durability of HBsAg loss. The nomogram illustrated its efficacy as a valuable instrument in showcasing survival probability of functional cure.

Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

BACKGROUND: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. METHODS: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. RESULTS: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. DISCUSSION: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

From tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF): perspectives in pediatric patients.

INTRODUCTION: Hepatitis B virus (HBV) affects hundreds of millions globally, with many cases stemming from perinatal transmission. Chronic hepatitis B (CHB) in children can progress to cirrhosis and hepatocellular carcinoma (HCC) in adulthood. Treatment options include interferons and nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs) such as tenofovir alafenamide (TAF). AREAS COVERED: This review covers the epidemiology of pediatric CHB and current treatments, with a focus on tenofovir-based therapies, particularly tenofovir disoproxil fumarate (TDF) and TAF. TDF has been used for years, but its risks of bone mineral density loss and renal impairment have raised concerns. TAF, with lower systemic exposure, appears to mitigate these risks. Ongoing trials are evaluating TAF's safety in younger children. There are knowledge gaps in long-term safety and the potential for combination therapies. EXPERT OPINION: TAF offers a safer alternative to TDF for children with CHB, showing high antiviral efficacy and fewer side effects. However, more data is needed on its use in younger children and long-term safety. The future of CHB treatment in pediatrics may include combination therapies and personalized approaches, potentially improving outcomes and minimizing risks over a lifetime of treatment. As research progresses, TAF is likely to become a cornerstone in pediatric CHB management.

Multiple Low-Level Viraemia Suggest Hindered Liver Fibrosis Regression in Chronic Hepatitis B Patients During Antiviral Therapy.

Low-level viraemia (LLV) occurs in chronic hepatitis B (CHB) patients despite antiviral treatment, which may cause failed histological regression. Our study aimed to investigate the impact of different LLV types on fibrosis regression. The prospective study enrolled CHB patients with paired liver biopsies before and after 260 weeks of entecavir treatment. Fibrosis regression was defined by the Ishak score or P-I-R system. Patients were grouped as the SVR (HBV DNA < 20 IU/mL persistently) or LLV (HBV DNA between 20 and 2000 IU/mL), which were further grouped as very low-level viraemia (VLLV, HBV DNA < 50 IU/mL), occasionally LLV (OLLV, HBV DNA ≥ 50 IU/mL only once) and multiple LLV (MLLV, HBV DNA ≥ 50 IU/mL more than once). Logistic regression models were used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). The analysis included 111 CHB patients. In the SVR group (n = 54), 39 (72.2%) patients had fibrosis regression, which was higher than the LLV (56.1%, p = 0.080). The fibrosis regression rates for VLLV (30 patients), OLLV (17 patients) and MLLV (10 patients) were 70.0%, 52.9% and 30.0%, respectively. Compared with SVR, VLLV (aOR = 0.78; 95% CI: 0.28-2.21; p = 0.644) was not associated with fibrosis regression, but patients with non-VLLV (aOR = 0.27; 95% CI: 0.09-0.85; p = 0.025), especially with MLLV (aOR = 0.19; 95% CI: 0.04-0.97; p = 0.046) is significantly associated with hindered fibrosis regression. Our study suggests that patients with detectable serum HBV DNA levels higher than 50 IU/mL need to be monitored carefully, especially in those with more than once. Trial Registration: ClinicalTrials.gov identifiers NCT01938781 and NCT01938820.

AI-Safe-C Score: Assessing Liver-Related Event Risks in Non-Cirrhotic Patients after Successful Direct-Acting Antiviral Treatment.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) have considerably improved chronic hepatitis C (HCV) treatment; however, post-sustained virological response (SVR) follow-up typically neglects the risk of liver-related events (LREs). This study introduces and validates artificial intelligence-safe score (AI-Safe-C score) to assess the risk of LREs in non-cirrhotic patients after successful DAA treatment. METHODS: The random survival forest model was trained to predict LREs in 913 non-cirrhotic HCV patients after SVR in Korea and was further tested in a combined cohort from Hong Kong and France (N = 1264). The model's performance was assessed using Harrell's C-index and the area under the time-dependent receiver operating characteristic curve (AUROC). RESULTS: The AI-Safe-C score, which incorporated liver stiffness measurement (LSM), age, sex, and six other biochemical tests-with LSM being ranked as the most important among 9 clinical features-demonstrated a C-index of 0.86 (95% confidence interval [CI]: 0.82-0.90) in predicting LREs in an external validation cohort. It achieved 3- and 5-year LRE AUROCs of 0.88 (95%CI, 0.84-0.92) and 0.79 (95%CI, 0.71-0.87), respectively, and for hepatocellular carcinoma, a C-index of 0.87 (95%CI, 0.81-0.92) with 3- and 5-year AUROCs of 0.88 (95%CI, 0.84-0.93) and 0.82 (95%CI, 0.75-0.90), respectively. Using a cut-off of 0.7, the 5-year LRE rate within a high-risk group was between 3.2% and 6.2%, mirroring the incidence observed in individuals with advanced fibrosis, in stark contrast to the significantly lower incidence of 0.2% to 0.6% in a low-risk group. CONCLUSION: AI-Safe-C score is a useful tool for identifying patients without cirrhosis who are at higher risk of developing LREs. The post-SVR LSM, as integrated within the AI-Safe-C score, plays a critical role in predicting future LREs. IMPACT AND IMPLICATIONS: The AI-Safe-C score introduces a paradigm shift in the management of non-cirrhotic patients post-DAA treatment, a cohort traditionally not included in routine surveillance protocols for LREs. By accurately identifying a subgroup at a comparably high risk of LREs, akin to those with advanced fibrosis, this predictive model facilitates a strategic reallocation of surveillance and clinical resources.

High efficacy and safety of direct-acting antivirals for the treatment of chronic hepatitis C: A cohort study conducted in Vietnam.

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha-fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well-tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies.

Interrelationships among MTHFR gene polymorphisms, MTRR gene polymorphisms, and HBV gene BCP 1762/1764 mutations with disease progression in Chronic hepatitis B virus infection patients.

OBJECTIVE: Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. METHODS: A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People's Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. RESULTS: The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). CONCLUSION: MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis.

BACKGROUND: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. RESULTS: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. CONCLUSIONS: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

Efficacy of short-term Peg-IFN α-2b treatment in chronic hepatitis B patients with ultra-low HBsAg levels: a retrospective cohort study.

PURPOSE: Peginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy. METHODS: In this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group. The Peg-IFN α-2b group received Peg-IFN α-2b for a minimum of 24 weeks, with the possibility of early discontinuation upon achieving HBsAg clearance, and were followed through week 48. The control group remained untreated for hepatitis B virus (HBV), and was observed for 24 weeks. HBsAg clearance rates were compared between groups. Univariate and multivariate logistic regression analyses were employed to identify factors associated with HBsAg clearance . RESULTS: By week 24, the HBsAg clearance rate in the Peg-IFN α-2b group was notably 52.1% (38/73), contrasting sharply with the mere 1.3% (1/77) observed in the control group. Within the Peg-IFN α-2b group, a substantial 97.3% (71/73) of patients noted a reduction in HBsAg levels. Besides, the decision to continue or discontinue treatment after the 24-week mark had no significant impact on the HBsAg clearance rate at week 48. Multivariable analysis pinpointed baseline HBsAg levels (OR = 0.984, p = 0.001) and the presence of fatty liver (OR = 5.960, p = 0.033) as independent predictors of HBsAg clearance. CONCLUSION: Our findings confirm that a 24-week course of Peg-IFN α-2b yields robust efficacy in CHB patients with ultra-low HBsAg levels. Prolonging treatment beyond the 24-week threshold is deemed unnecessary. Both baseline HBsAg level and the presence of fatty liver emerged as significant predictors for HBsAg clearance.

Preclinical and clinical antiviral characterization of AB-836, a potent capsid assembly modulator against hepatitis B virus.

HBV capsid assembly modulators (CAMs) target the core protein and inhibit pregenomic RNA encapsidation and viral replication. HBV CAMs also interfere with cccDNA formation during de novo infection, which in turn suppresses transcription and production of HBV antigens. In this report, we describe the antiviral activities of AB-836, a potent and highly selective HBV CAM. AB-836 inhibited viral replication (EC50 = 0.010 µM) in HepDE19 cells, and cccDNA formation (EC50 = 0.18 µM) and HBsAg production (EC50 = 0.20 µM) in HepG2-NTCP cells during de novo infection. AB-836 showed broad genotype coverage, remained active against variants resistant to nucleos(t)ide analogs, and demonstrated improved antiviral potency against core variants resistant to other CAMs. AB-836 also mediated potent inhibition of HBV replication in a hydrodynamic injection mouse model, reducing both serum and liver HBV DNA. In a Phase 1 clinical study, 28 days of once-daily AB-836 oral dosing at 50, 100, and 200 mg resulted in mean serum HBV DNA declines of 2.57, 3.04, and 3.55 log10 IU/mL from baseline, respectively. Neither on-treatment viral rebound nor the emergence of viral resistance was observed during the 28-day treatment period. Furthermore, HBV DNA sequence analysis of baseline samples from the Phase 1 study revealed that 51.4% of the chronic hepatitis B participants contained at least one core polymorphism within the CAM-binding pocket, suggesting that genetic variations exist at this site. While AB-836 was discontinued due to clinical safety findings, data from the preclinical and clinical studies could help inform future optimization of HBV CAMs.

Concurrent HBsAg and anti-HBs induced by a preS deletion mutant in a chronic hepatitis B patient.

This study analyzed the origins of concurrent hepatitis B surface antigen (HBsAg) and HBsAg antibodies (anti-HBs) in a patient with chronic hepatitis B virus (HBV) infection. The levels of serological markers of HBV infection were determined by enzyme-linked immunosorbent assay (ELISA). The preS/S gene was analyzed by gene amplification and sequencing. The tests revealed that HBsAg and anti-HBs coexisted in this patient with mixed infections of the full-length preS/S virus strain and preS1 183 bp deletion mutant, and both the mutant and the anti-HBs were no longer present after one year, which means that the mutant strain was cleared by the detected antibodies. Thus, it is speculated that anti-HBs antibodies targeted specifically to the preS1 deletion mutant strain instead of the strain with the full-length large S protein were produced. This mechanism is quite different from other immunopathogenic mechanisms for concurrent HBsAg and anti-HBs.

Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C Shows Liver Fibrosis Regression on Three Noninvasive Tests: A Puerto Rican Cohort.

OBJECTIVE: Direct-acting antiviral (DAA) drugs have resulted in high rates of virological cure in chronic hepatitis C (CHC)-infected patients. We used noninvasive tests to assess fibrosis in subjects who had been cured with DAA. METHODS: Retrospective data collection (2014-2019) from the medical record of CHC patients at the hepatology clinic was performed. Subjects co-infected with HIV and hepatitis B, post-liver transplant, and lost to follow-up were excluded. We evaluated fibrosis at baseline and 1 year after completing therapy using vibration-controlled transient elastography (VCTE), fibrosis-4 (FIB-4), and aspartate aminotransferase-toplatelet ratio index (APRI) scores. RESULTS: With 210 medical records reviewed, 41 were included. The mean age was 62.8 years; 61% were men. Significant fibrosis regression was observed 1-year post-treatment using 3 noninvasive methods: VCTE, APRI, and FIB-4 score. Prior to treatment, 46% of the patients had advanced fibrosis compared to 25% 1 year after treatment. The VCTE scores of 4 subjects (with body mass indices [BMIs] > 30) indicated a worsening of fibrosis. We did not find a statistically significant association between BMI and VCTE, FIB-4, or APRI score. CONCLUSION: In most CHC patients, DAA therapy leads to liver fibrosis regression. Obesity may play an important role in the worsening of hepatic fibrosis or the absence of fibrosis regression.

Comorbidities and Monitoring in Patients with Chronic Hepatitis B on Nucleos(t)ide Analogues Attending a Tertiary Hospital in Malaysia, Southeast Asia: A Critical Perspective.

Background: Chronic hepatitis B (CHB) is a significant global public health concern in Malaysia. It is a potentially life-threatening liver disease caused by the hepatitis B virus (HBV), which can lead to long-term complications such as cirrhosis, liver failure and hepatocellular carcinoma. In managing CHB, nucleos(t)ide analogues (NAs) have become the preferred treatment due to their ability to suppress viral replication and prevent disease progression. The question of liver-associated comorbidities related to patients with CHB on NAs remains unresolved in Malaysia despite the impending burden of CHB in the country. This study intends to address this and related aspects. Method: We assessed 136 CHB patients on NAs in one centre, the Hospital Universiti Sains Malaysia. Demographic and epidemiological data on the treatment, concomitant disease and monitoring strategies were collected and analysed. Result: Patients on NAs aged 50 years old-70 years old had the highest proportion of CHB (45.59%), with males representing 61.03% of that age group. There was a statistical significance in CHB acquisition and presence of comorbidities at P > 0.005. Our cohort displayed seven comorbidities (diabetes, obesity, rheumatoid diseases, renal impairment, spontaneous bacterial peritonitis, hypertension, non-hepatocellular malignancies and carcinoma); hypertension had the highest incidence (69.12%), while renal impairment had the lowest incidence (8.09%). Whole blood count, liver function and creatinine tests were the major monitoring tests used in over 90% of the cohort compared to viral load (6.1%). Conclusion: Diabetes, hypertension and obesity were independent risk factors for acquiring liver cirrhosis and hepatocellular carcinoma. Malaysian CHB patients treated with NAs have several comorbidities that could affect disease outcomes. Therefore, careful monitoring is required.

Plasma microRNA-15a/16-1 serves as a non-invasive indicator of liver fibrosis severity in individuals with chronic hepatitis B.

Background: The lack of effective non-invasive diagnostic methods for liver fibrosis hinders timely treatment for chronic hepatitis B (CHB) patients, leading to the progression of advanced liver disease. Circulating microRNAs offer a non-invasive approach to fibrosis assessment. MicroRNA-15a/16-1 (miR-15a/16) was reported to be implicated in fibrosis development, but the role of plasma miR-15a/16 in liver fibrosis assessment remains poorly understood. This study explored the importance of plasma miR-15a/16 in assessing liver fibrosis severity of CHB patients. Methods: Quantitative PCR was utilized to measure the levels of plasma miR-15a/16 in 435 patients with CHB and 74 healthy controls. We assessed the correlation between plasma miR-15a/16 levels and liver fibrosis and cirrhosis using Pearson correlation coefficients, multivariate linear and logistic regression models, and smooth curve fitting. Utilizing the receiver operating characteristic (ROC) curve, we examined the diagnostic potential of plasma miR-15a/16 in severe fibrosis and cirrhosis. Results: Plasma levels of miR-15a/16 in patients with CHB were significantly reduced compared to those in healthy controls. In the CHB cohort, levels were notably decreased in individuals with severe fibrosis or cirrhosis compared to those without severe fibrosis or cirrhosis. Plasma miR-15a/16 levels exhibited a negative relationship with the severity of liver fibrosis, gradually decreasing as the histological fibrosis stage progressed from S0 to S4. Reduced levels of plasma miR-15a/16 were linked to an elevated risk of severe liver fibrosis (miR-15a: odds ratio [OR] = 0.243; 95 % confidence interval [CI]: 0.138, 0.427; miR-16: OR = 0.201; 95 % CI: 0.097, 0.417) and cirrhosis (miR-15a: OR = 0.153; 95 % CI: 0.079, 0.298; miR-16: OR = 0.064; 95 % CI: 0.025, 0.162). MiR-15a achieved an area under the ROC curve of 0.886 and 0.832 for detecting moderate-to-severe fibrosis (S2-S4) and cirrhosis, respectively. MiR-16 demonstrated similar diagnostic values. Conclusion: Plasma miR-15a/16 levels were negatively correlated with the severity of liver fibrosis in CHB patients and could serve as a new non-invasive indicator in evaluating liver fibrosis.

Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.

BACKGROUND/AIM: Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). METHODS: We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. RESULTS: Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. CONCLUSION: TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

CXCR7 genetic variant predicts treatment response of pegylated-interferon α in HBeAg-positive chronic hepatitis B patients.

OBJECTIVES: CXC chemokine receptor 7 (CXCR7) plays pivotal roles in different virus infections. However, no research focused on the role of CXCR7 in hepatitis B virus (HBV)-infected patients. The primary aim of this study is to elucidate the role of CXCR7 in predicting the treatment response of chronic hepatitis B (CHB) patients undergoing pegylated interferon-alpha (PegIFNα) therapy. METHODS: Two cohorts with a total of 945 Chinese CHB patients (Cohort 1, n = 238; Cohort 2, n = 707) were enrolled in this retrospective study, all the patients were positive for hepatitis B e antigen (HBeAg) and received PegIFNα treatment for 48 weeks and followed-up for 24 weeks post-treatment. Nineteen tag single-nucleotide polymorphisms (SNPs) were selected within and surrounding the CXCR7 gene region. The associations of CXCR7 SNPs and polygenic score (PGS) with PegIFNα treatment response were investigated in the two cohorts. RESULTS: Among the 19 candidate SNPs of CXCR7, rs2952665 (A > G) was significantly associated with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <3.3log10IU/mL, P = 0.002) and hepatitis B surface antigen (HBsAg) decline (P = 0.015) in the two cohorts at week 72. Furthermore, a PGS comprising CXCR7_rs2952665 and five additional SNPs, which were previously recognized as biomarkers of PegIFNα treatment response, demonstrated a robust correlation with both CR (P = 1.38 × 10-12) and HBsAg decline (P = 0.003) in all the patients. CONCLUSION: This research illustrated that CXCR7_rs2952665 is a promising predictor of the PegIFNα therapy efficiency in Chinese HBeAg-positive CHB patients. A PGS consisting of CXCR7_rs2952665 and five previously reported SNPs predicts treatment response to PegIFNα better.