New antiviral agents are needed for the treatment of hepatitis B virus (HBV) infection because currently available drugs do not completely eradicate chronic HBV in patients. Phosphorylation dynamics of the HBV core protein (HBc) regulate several processes in the HBV life cycle, including nucleocapsid formation, cell trafficking, and virus uncoating after entry. In this study, the SRPK inhibitors SPHINX31, SRPIN340, and SRPKIN-1 showed concentration-dependent anti-HBV activity. Detailed analysis of the effects of SRPKIN-1, which exhibited the strongest inhibitory activity, on the HBV replication process showed that it inhibits the formation of infectious particles by inhibiting pregenomic RNA packaging into capsids and nucleocapsid envelopment. Mass spectrometry analysis combined with cell-free translation system experiments revealed that hyperphosphorylation of the C-terminal domain of HBc is inhibited by SRPKIN-1. Further, SRPKIN-1 exhibited concentration-dependent inhibition of HBV infection not only in HepG2-hNTCP-C4 cells but also in fresh human hepatocytes (PXB cells) and in the single-round infection system. Treatment with SRPKIN-1 at the time of infection reduced the nuclease sensitivity of HBV DNA in the nuclear fraction. These results suggest that SRPKIN-1 has the potential to not only inhibit the HBV particle formation process but also impair the early stages of viral infection.

Rifaximin, a non-absorbable antibiotic, has been demonstrated to be effective against hepatic encephalopathy (HE); however, its efficacy on liver functional reserve remains unknown. Here, we evaluated the efficacy of rifaximin on the liver functional reserve and serological inflammation-based markers in patients with cirrhosis. A retrospective study was conducted on patients who received rifaximin for more than three months at our hospital between November 2016 and October 2021. The recurrence and grade of HE, serological ammonia levels, Child–Pugh score (CPS), and serological inflammation-based markers such as the neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), platelet–lymphocyte ratio (PLR), C-reactive protein (CRP), and CRP to albumin ratio (CAR) were evaluated. The correlations between serological inflammation-based markers and liver functional reserve were evaluated. HE grades, serum ammonia levels, and inflammation-based markers significantly improved at three months compared with those at baseline. Patients with improved albumin levels showed significantly higher CRP improvement rates at both 3 and 12 months. Patients with an improvement in CAR at 3 months demonstrated a significant improvement in CPS at 12 months. Rifaximin improved the liver functional reserve in patients with cirrhosis. Improvements in inflammation-based markers, particularly CRP and albumin, may be involved in this process.

Background and Aims. To examine the changes in serum alpha-fetoprotein (AFP) levels after iron reduction by therapeutic phlebotomy in chronic hepatitis C patients.Methods. This retrospective study included 26 chronic hepatitis C patients. The patients were developed iron depletion by repeated therapeutic phlebotomies.Results. Iron reduction therapy significantly reduced the median level of serum AFP from 13 to 7 ng/mL, ALT from 96 to 50 IU/L, gamma-glutamyl transpeptidase (GGT) from 55 to 28 IU/L, and ferritin from 191 to 10 ng/mL (P<0.001for each). The rate of decline in the AFP level correlated positively only with that in GGT(r=0.695, P=0.001), although a spurious correlation was observed between the rates of decline for AFP and ALT. The AFP level normalized (<10 ng/mL) posttreatment in eight (50%) of 16 patients who had elevated pretreatment AFP levels. Normalized post-treatment ALT and GGT levels were seen in 12% (3 of 26) and 39% (7 of 18) of the patients, respectively. Multivariate analysis identified a post-treatment GGT level of <30 IU/L as an independent factor associated with post-treatment AFP normalization (odds ratio, 21; 95% confidence interval, 1.5–293;P=0.024).Conclusions. Iron reduction by therapeutic phlebotomy can reduce serum AFP and GGT levels in chronic hepatitis C patients.