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Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials

Buti, Maria; Lim, Young-Suk; Chan, Henry Lik Yuen; Agarwal, Kosh; Marcellin, Patrick; Brunetto, Maurizia R; Chuang, Wan-Long; Janssen, Harry L A; Fung, Scott K; Izumi, Namiki; Jablkowski, Maciej S; Abdurakhmanov, Dzhamal; Abramov, Frida; Wang, Hongyuan; Botros, Irina; Yee, Leland J; Mateo, Roberto; Flaherty, John F; Osinusi, Anu; Pan, Calvin Q; Shalimar, X; Seto, Wai-Kay; Gane, Edward J
BACKGROUND:In two phase 3 studies, tenofovir alafenamide (TAF) showed non-inferior efficacy versus tenofovir disoproxil fumarate (TDF), with more favourable renal and bone safety in patients with chronic hepatitis B (CHB). AIMS/OBJECTIVE:Here, we report the studies' final 8-year results. METHODS:CHB patients (hepatitis B e antigen [HBeAg]-negative and HBeAg-positive) were randomised (2:1) to double-blind TAF 25 mg/day or TDF 300 mg/day for up to 3 years, followed by open-label (OL) TAF through year 8. Virological, biochemical, serological and fibrosis responses, and safety, including bone and renal parameters, were evaluated. Resistance to TAF was assessed annually by deep sequencing of polymerase/reverse transcriptase and by phenotyping. RESULTS:and hip/spine BMD observed during double-blind TDF improved after switching to OL TAF. No patients developed resistance to TAF. CONCLUSION/CONCLUSIONS:Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance. CLINICALTRIALS/RESULTS:gov numbers NCT01940341 and NCT01940471.
PMCID:11599788
PMID: 39327857
ISSN: 1365-2036
CID: 5763322

Clinical Characteristics of Sarcopenia in Nonalcoholic Fatty Liver Disease: A Systemic Scoping Review

Ye, Tingdan; Mi, Ke; Zhu, Lin; Li, Jonathan; Pan, Calvin Q
INTRODUCTION/BACKGROUND:This systematic scoping review aimed to synthesize existing research findings on the clinical manifestations in patients with nonalcoholic fatty liver disease (NAFLD) and sarcopenia. METHODS:Adhering to scoping review guidelines, we comprehensively searched five databases for literature on sarcopenia's clinical manifestations in NAFLD patients from December 2013 to December 2023, meticulously compiling and synthesizing the findings. RESULTS:A total of 312 articles were identified, with 9 studies included in the final review. Of these, 90% were cross-sectional investigations, with 70% from Asian cohorts. Comparative analysis between patients solely afflicted with NAFLD and those additionally experiencing sarcopenia revealed discernible trends. Individuals with both conditions tended to be older, have a higher body mass index, and show a higher prevalence among females, underscoring the influence of unhealthy lifestyles and obesity. Furthermore, comorbidities like metabolic syndrome, hypertension, and diabetes have been implicated in sarcopenia manifestation among NAFLD patients. Nonetheless, the lack of standardized diagnostic criteria and patterns poses an ongoing clinical challenge for this subgroup. CONCLUSIONS:Our review highlights distinct clinical characteristics evident in NAFLD patients with sarcopenia. However, comprehensive investigations remain scarce, impeding accurate early detection and intervention. Future research should prioritize bridging these gaps and fostering enhanced clinical management strategies.
PMID: 39413746
ISSN: 1662-4033
CID: 5766612

Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate for Preventing Vertical Transmission in Chronic Hepatitis B Mothers: A Systematic Review and Meta-Analysis

Pan, Calvin Q; Zhu, Lin; Yu, Andy S; Zhao, Yuchan; Zhu, Bo; Dai, Erhei
OBJECTIVE:International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. DESIGN/METHODS:In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. RESULTS:We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. CONCLUSION/CONCLUSIONS:Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.
PMID: 38805690
ISSN: 1537-6591
CID: 5663442

Clinical Features and Long-Term Outcomes of Patients Diagnosed with MASLD, MAFLD, or Both [Letter]

Zhou, Xiao-Dong; Lonardo, Amedeo; Pan, Calvin Q; Shapiro, Michael D; Zheng, Ming-Hua; ,
PMID: 38554846
ISSN: 1600-0641
CID: 5645412

The new nomenclature SLD and categories provided better classification for elderly Chinese with liver steatosis [Letter]

Qiu, Lixia; Zhang, Shuang; Zhang, Yang; Pan, Calvin Q; Zhang, Jing
PMID: 38704293
ISSN: 1879-0828
CID: 5658282

Letter: Boosting non-invasive tests-Opportunities and challenges from resmetirom [Comment]

Feng, Gong; Pan, Calvin Q; Zheng, Ming-Hua
PMID: 38709140
ISSN: 1365-2036
CID: 5732172

Performance of MAST, FAST, and MEFIB in predicting metabolic dysfunction-associated steatohepatitis

Qi, Shi; Wei, Xiaodie; Zhao, Jinhan; Wei, Xinhuan; Guo, Haiqing; Hu, Jingxian; WuYun, Qiqige; Pan, Calvin Q; Zhang, Nengwei; Zhang, Jing
BACKGROUND AND AIM/OBJECTIVE:To identify individuals with metabolic dysfunction-associated steatohepatitis (MASH) or "at-risk" MASH among patients with metabolic dysfunction-associated steatotic liver disease (MASLD), three noninvasive models are available with satisfactory efficiency, which include magnetic resonance imaging [MRI]- AST (MAST), FibroScan-AST (FAST score), and magnetic resonance elastography [MRE] plus FIB-4 (MEFIB). We aimed to evaluate the most accurate approach for diagnosing MASH or "at-risk" MASH. METHODS:We included 108 biopsy-proven MASLD patients who underwent simultaneous assessment of MRE, MRI proton density fat fraction (MRI-PDFF), and FibroScan scans. Compared with the histological diagnosis, we analyzed the AUC of each model and assessed the accuracy. RESULTS:Our study cohort consisted of 64.8% of MASH and 25.9% of "at-risk" MASH. When analyzing the performance of each model for the diagnostic accuracy of MASH, we found that the AUC [95% CI] of MAST was comparable to FAST (0.803 [0.719-0.886] vs 0.799 [0.707-0.891], P = 0.930) and better than MEFIB (0.671 [0.571-0.772], P = 0.005). Similar findings were observed in the "at-risk" MASH patients. The AUCs [95% CI] for MAST, FAST, and MEFIB were 0.810 [0.719-0.900], 0.782 [0.689-0.874], and 0.729 [0.619-0.838], respectively. The models of MAST and FAST had comparable AUCs (P = 0.347), which were statistically significantly higher than that of MEFIB (P = 0.041). Additionally, the cutoffs for diagnosis of MASH were lower than "at-risk" MASH. CONCLUSION/CONCLUSIONS:MAST and FAST performed better than MEFIB in diagnosing "at-risk" MASH and MASH using lower cutoff values. Our findings provided evidence for selecting the most accurate noninvasive model to identify patients with MASH or at-risk MASH.
PMID: 38686620
ISSN: 1440-1746
CID: 5658022

Comparison of Autolumo A2000 Plus and Architect i2000 for detection of hepatitis B virus serological markers

Zhang, Xue-Dong; Song, Xue-Dong; Lu, Jian-Hua; Dai, Yan; Li, Bin; Zhu, Ping; Dai, Er-Hei; Pan, Calvin Q; Chen, Wei
Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p < 0.0001. HBV marker consistency test results show perfect consistency between the two analyzers, with Kappa values ranging from 0.854 to 1.000. For specific samples, including Hepatitis B patients with Genotype C, chronic hepatitis B, hepatitis B-related cirrhosis, and hepatocellular carcinoma, spearman correlation analysis showed HBsAg correlation coefficients ranging from 0.8532 to 0.9745, p < 0.001 in both analyzers. In conclusion, Autolumo A2000Plus diagnostic performance in consistency and correlation is comparable to Abbott Architect i2000 when detecting markers of hepatitis B infection. The Autolumo A2000Plus system can be used as a reliable instrument for HBV marker detection.
PMCID:11304000
PMID: 39113996
ISSN: 2405-8440
CID: 5730792

Novel Approach: Maternal TAF Prophylaxis to Prevent HBV Transmission

Pan, Calvin Q; Zhu, Bo; Ye, Tingdan; Dai, Erhei
PMID: 38985092
ISSN: 1537-6591
CID: 5732352

Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes? [Editorial]

Huang, Chen-Xiao; Zhou, Xiao-Dong; Pan, Calvin Q; Zheng, Ming-Hua
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.
PMCID:11212714
PMID: 38947289
ISSN: 2219-2840
CID: 5732652