Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial.

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.

A single nucleotide polymorphism CTSB rs12898 is associated with primary hepatic cancer in a Chinese population.

BACKGROUND & AIMS: Primary hepatic cancer (PHC) is a common malignant tumor and the third most frequent cause of cancer-related death worldwide. However, the molecular mechanisms underlying hepatic cancer remain unknown. CTSB is considered a biomarker of cancer as it can facilitate tumor progression. We aimed to investigate the association between genetic polymorphisms of potential regulatory SNPs in the CTSB gene and PHC. METHODS: The relationship between CTSB rs12898 and PHC was analyzed in a case-control study with a Chinese population of 608 PHC patients and 608 healthy individuals using SPSS 21.0. RESULTS: PHC was significantly associated with alcohol consumption (P < 0.001), history of hepatitis (P < 0.001), and liver cirrhosis (P < 0.001), but not with smoking (P = 0.168), age (P = 0.175), or sex (P = 0.051). Distribution of three genotypes (GG, GA, and AA) of CTSB rs12898 significantly differed between the cases and controls (P < 0.001). Compared with the GG genotype, the GA and AA genotype was associated with a significantly increased risk of PHC (OR = 1.425, 95% CI = 1.099-1.848, P = 0.007; and OR = 2.220, 95% CI = 1.574-3.132, P < 0.001, respectively). CTSB rs12898 was associated with a significantly increased risk of PHC under a dominant model (OR = 1.592, 95% CI = 1.243-2.040, P < 0.001), and under a recessive model (OR = 1.771, 95% CI = 1.311-2.393, P < 0.001) for the variant A allele. CONCLUSION: Results suggest that CTSB rs12898G > A may play a role in the pathogenesis of PHC, and may be a marker for susceptibility to PHC.