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Genetic variation in UDP-glucuronosyltransferase 1A1 gene (UGT1A1) is a lithogenic risk factor for gallstone formation. This study aimed to assess genotype and allele frequencies of common UGT1A1 variants in patients with gallstone and hepatitis B virus (HBV)-related hepatic failure. This study enrolled 113 healthy individuals (CTRL), 54 patients with HBV infection (HBV), 134 patients with gallstone-free hepatic failure and HBV infection, and 34 patients with gallstone-related hepatic failure and HBV infection (GRHF). Peripheral venous blood samples were collected for genomic DNA isolation. Polymerase chain reaction amplification was carried out for UGT1A1, followed by direct sequencing. Analysis for genotype and allele frequencies of UGT1A1 variants (UGT1A1*6, UGT1A1*27, UGT1A1*28, and UGT1A1*60) was performed. The allele distributions of the four groups did not deviate from Hardy–Weinberg equilibrium. Allele (A) and genotype (CA) frequency distributions of UGT1A1*27 were significantly different between GRHF and CTRL, or between GRHF and HBV. GRHF and CTRL exhibited significant differences in allele (A) and genotype (CA) frequency distributions of UGT1A1*28. Linkage disequilibrium analysis suggested that haplotype G-G-[TA]7-T may be associated with gallstone in HBV-related hepatic failure. Our data reveal that UGT1A1*27 and UGT1A1*28 variants are significantly observed in patients with GRHF compared to healthy individuals.

Background Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. Methods Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. Results A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group. Conclusions Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated. Clinical Trials registration NCT00230503 and China Drug Trials CTR2018042 [ABSTRACT FROM AUTHOR]

Summary: Background: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). Aim: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). Methods: We performed a randomised, double‐blind, non‐inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. Results: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non‐inferiority criterion was met in all analysis sets. In the HBeAg‐positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg‐negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. Conclusion: TMF was non‐inferior to TDF in terms of anti‐HBV efficacy and showed better bone and renal safety. (NCT03903796). [ABSTRACT FROM AUTHOR]

Background and Aims: Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results., Methods: Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters., Results: Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group ( p =0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend., Conclusions: TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796)., Competing Interests: ZL has served as a speaker for Bristol Myers Squibb (BMS), Gilead Sciences, and Hansoh Pharma. QJ has served as a speaker for Abbott, Amoytop Biotech, Chiatai Tianqing, Gilead, and has received research funding from Kawin Technology, Chiatai Tianqing, Hansoh Pharma, Johnson and Johnson (J&J), BMS, HEC Pharmaceutical, TaiGen Biotechnology, Gilead Science. JN has served as a speaker for and has received research funding from HEC Pharmaceutical, Xintong Pharmacy, Hansoh Pharma, Qilu Pharmaceutical, Kelun Industry, Roche, J&J, GlaxoSmithKline (GSK), Assembly, Gilead, Brii Biosciences, Huahui Health, Zhimeng Biopharma, Hengrui Medicine, Aligos, Hepu Pharmaceutical, Ascletis Pharma, Sanhome, Ginkgo pharma, Changzhou Yinsheng pharma. JH has received consulting fee from AbbVie, Arbutus, BMS, Gilead Sciences, J&J, Roche and received grants from BMS and J&J. QW, CP, WJ, CL, and CS are employees of Hansoh Pharmaceuticals Co., Ltd. JN has has been an associate editor of Journal of Clinical and Translational Hepatology since 2013, and JH has has been an executive associate editor of Journal of Clinical and Translational Hepatology since 2021. The other authors have no conflict of interests related to this publication., (© 2023 Authors.)

The aim of the present study was to identify monitoring and prevention measures as well as predictive factors for early detection of renal toxicity associated with long-term administration of adefovir dipivoxil in order to avoid progression to Fanconi syndrome. Clinical data of 28 patients with Fanconi syndrome caused by long-term administration of adefovir dipivoxil for the treatment of chronic hepatitis B virus (HBV) infection were collected pre-and post-administration for analysis. Patients presented with fatigue, progressive systemic pain in multiple bones and joints, as well as difficulty in walking and pathological fractures in a number of severe cases. Laboratory examinations revealed hypophosphatemia, elevated serum cystatin C (Cys-C), elevated serum creatinine (SCr), reduced glomerular filtration rate (GFR), positive urinary protein, erythrocytes and glucose, as well as osteoporosis. In consequence, adefovir dipivoxil administration was stopped, and patients received concentrated divitamins, sodium phosphate syrup and calcitriol. Symptoms and abnormalities in laboratory examinations were significantly improved in all patients after 2-6 months. Therefore, serum phosphate, SCr, routine urine parameters, Cys-C and GFR should be monitored regularly in chronic HBV patients treated with adefovir dipivoxil. The following factors were identified as predictive of kidney damage and Fanconi syndrome: Age ≥40 years, living in rural areas, previous renal toxicity, estimated GFR (eGFR) <90 ml/min/1.73 m 2 , hypertension, diabetes, cirrhosis and duration of adefovir dipivoxil treatment exceeding 24 months. The present results indicate that timely termination of adefovir dipivoxil treatment and replacement with other antiviral agents is critical once renal impairment appears, and that it is necessary to change to other antiviral agents and prolong the interval of administration according to the eGFR level.