OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

OBJECTIVES: To evaluate whether adding Fuzheng Jiedu Xiaoji (FZJDXJ) therapy improves survival in advanced hepatitis B virus-related HCC (HBV-HCC) patients. METHODS: This prospective, randomized controlled study was performed at a major academic medical center in Beijing, China from October 2020 to October 2022. Eligible patients with advanced HBV-HCC were randomly divided equally (1:1) to receive either the combination of FZJDXJ and conventional Western medical therapy (63 cases, FZJDXJ group) or solely Western medicine (66 cases, control group). The study endpoints consisted of overall survival (OS) as the primary outcome, with progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs) as secondary measures. RESULTS: The median OS was significantly prolonged in the FZJDXJ group at 8.9 months (95% CI: 6.0-11.9) vs. 4.4 months (95% CI: 3.2-7.3) in the control group (P<0.05). The hazard ratio for mortality in the FZJDXJ group was 0.59 (95% CI: 0.40-0.89), suggesting a 41% lower risk of death compared to the control group. The results revealed that patients receiving FZJDXJ therapy achieved a PFS of 5.1 months (95% CI: 4.1 to 7.2 months), compared to only 2.9 months (95% CI: 2.0 to 4.6 months) in the control group (P<0.05). Additionally, DCR was significantly elevated in the FZJDXJ group (20.6%) compared to the control group (10.6%, P<0.05). Subgroup analysis demonstrated that FZJDXJ significantly improved OS in patients with alpha-fetoprotein levels <400 ng/mL, age <60 years, Barcelona Clinic Liver Cancer (BCLC) stage C, and compensated liver function (Child-Pugh A and B, P<0.05). Multivariate analysis revealed that FZJDXJ therapy acted as an independent factor protecting against mortality within 1 year. Gastrointestinal symptoms are rare side effects, and no fatalities associated with the treatment were reported. CONCLUSION This randomized controlled trial demonstrated that FZJDXJ combined Western conventional therapy significantly improves OS and PFS in patients with advanced HBV-HCC. (registration No. ChiCTR2000033941).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/virology* ; Carcinoma, Hepatocellular/virology* ; Treatment Outcome ; Hepatitis B virus ; Adult ; Aged ; Hepatitis B/drug therapy*

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

Objective:b> To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods:b> Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results:b> 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion:b> Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*

To prepare the herpetolide A nanosuspension lyophilized powder(HPA-NS-LP), in order to investigate its anti-hepatitis B virus(HBV) activity and the dissolution in vitro. Herpetolide A nanosuspension(HPA-NS) was prepared by ultrasonic precipitation method. The formulation and process of HPA-NS were optimized by the single factor experiment. Lyophilized powder(HPA-NS-LP) was prepared by freeze-drying method. Scanning electron microscopy was used to observe morphology of HPA-NS-LP. Paddle method was used to determinate the dissolution of HPT-NS-LP in vitro. The anti-HBV activity of herpetolide A coarse suspension lyophilized powder(HPA-CS-LP) and HPA-NS-LP was evaluated by HepG2.2.15 cell model. The mean particle size of optimized HPA-NS was(173.46±4.36) nm, with a polydispersity index of 0.110±0.012. After redispersion, the mean particle size and the polydispersity index of HPA-NS-LP increased, with changes within a rational range. Scanning electron microscopy showed that HPA-NS-LP was spherical in shape. Cumulative dissolution rate of HPA-NS-LP was more than 90% in 2 hours, which was higher than that of HPA-CS-LP. Both HPA-CS-LP and HPA-NS-LP could effectively inhibit the secretion of HepG2.2.15 cell antigens(HBsAg and HBeAg), and the inhibitory effect of HPA-NS-LP was significantly higher than that of HPA CS-LP(P<0.05). HBV-DNA test showed that high, medium and low-dose HPA-NS-LP(50, 25, 12.5 mg·kg~(-1)) significantly decreased the level of HBV-DNA(P<0.05), and the effect was better than that of the same dose of HPA-CS-LP(P<0.05). The results revealed that HPA-NS-LP exhibited anti-HBV activity in vitro, and its effect was superior to that of HPA-CS-LP.
Coumarins/pharmacology* ; Cucurbitaceae/chemistry* ; Hep G2 Cells ; Hepatitis B virus/drug effects* ; Humans ; Nanoparticles ; Particle Size ; Phytochemicals/pharmacology* ; Solubility ; Suspensions

OBJECTIVE: To evaluate the therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels. METHODS: We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)]. RESULTS: In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( < 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( < 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( < 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- group, the rates were also similar between subgroups 1 and 2 (30.6% 33.3%, > 0.05); but the rates differed significantly between the same subgroups with different treatments ( < 0.05). CONCLUSIONS In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (> 5 × ULN) show better responses to both ETV and IFN- treatment than those with ALT level below 5×ULN. We thus recommend IFN- for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.
Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; drug therapy ; enzymology ; immunology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Viral Load ; drug effects

BACKGROUND/AIMS: Hepatitis B virus reactivation (HBVr) following chemotherapy (CMT) is well-known among hematologic malignancies, and screening recommendations are established. However, HBVr data in solid organ malignancy (SOM) patients are limited. This study aims to determine hepatitis B surface antigen (HBsAg) screening rates, HBV prevalence, and the rate of significant hepatitis caused by HBVr in SOM patients undergoing CMT.METHODS: Based on the Oncology unit’s registration database from 2009–2013, we retrospectively reviewed records of all SOM patients ≥18 years undergoing CMT at Songklanagarind Hospital who were followed until death or ≥6 months after CMT sessions. Exclusion criteria included patients without baseline liver function tests (LFTs) and who underwent CMT before the study period. We obtained and analyzed baseline clinical characteristics, HBsAg screening, and LFT data during follow-up.RESULTS: Of 3,231 cases in the database, 810 were eligible. The overall HBsAg screening rate in the 5-year period was 27.7%. Screening rates were low from 2009–2012 (7.8–21%) and increased in 2013 to 82.9%. The prevalence of HBV among screened patients was 7.1%. Of those, 75% underwent prophylactic antiviral therapy. During the 6-month follow-up period, there were three cases of significant hepatitis caused by HBVr (4.2% of all significant hepatitis cases); all were in the unscreened group.CONCLUSIONS: The prevalence of HBV in SOM patients undergoing CMT in our study was similar to the estimated prevalence in general Thai population, but the screening rate was quite low. Cases of HBVr causing significant hepatitis occurred in the unscreened group; therefore, HBV screening and treatment in SOM patients should be considered in HBV-endemic areas.
Asian Continental Ancestry Group ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Follow-Up Studies ; Hematologic Neoplasms ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis ; Humans ; Liver Function Tests ; Mass Screening ; Prevalence ; Retrospective Studies ; Thailand ; Virus Activation

<b>BACKGROUNDb>Tenofovir disoproxil (TDF) is a promising salvage therapy for patients with chronic hepatitis B (CHB) who failed regimens of other nucleoside analogues (NAs). In this study, we aimed to investigate the clinical efficacy and safety of TDF monotherapy in Chinese CHB patients with genotypic resistance.

<b>METHODSb>A total of 33 CHB patients who had failed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients' demographic data (age, sex, history of hepatitis B virus [HBV] therapy), laboratory testing results (hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay), clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 (baseline) and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation.

<b>RESULTSb>With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability (rs = 0.39, P = 0.030). ALT levels were normal in 30 of 33 patients (91%). HBeAg negative conversion occurred in 7 of 25 patients (28%), among whom HBeAg seroconversion (12%) and HBeAg seroclearance (16%) occurred. The time of complete virological response was significantly affected by the number of resistance loci (rs = 0.36, P = 0.040). Concerning safety, the study found that no adverse events were observed during the 48 weeks.

<b>CONCLUSIONb>TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.

Adult ; Anti-HIV Agents ; adverse effects ; therapeutic use ; DNA, Viral ; genetics ; Drug Resistance, Viral ; Female ; Genotype ; Hepatitis B virus ; drug effects ; pathogenicity ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Tenofovir ; adverse effects ; therapeutic use

<b>BACKGROUNDb>The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.

<b>METHODSb>One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.

<b>RESULTSb>Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2).

<b>CONCLUSIONb>This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.

<b>TRIAL REGISTRATIONb>ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.

Adult ; Alanine Transaminase ; metabolism ; Anti-HIV Agents ; therapeutic use ; Aspartate Aminotransferases ; metabolism ; Benzoxazines ; therapeutic use ; CD4-Positive T-Lymphocytes ; metabolism ; Coinfection ; drug therapy ; Female ; HIV Infections ; drug therapy ; Hepatitis B virus ; drug effects ; pathogenicity ; Humans ; Lamivudine ; therapeutic use ; Male ; Tenofovir ; therapeutic use

<b>BACKGROUNDb>The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China.

<b>METHODSb>From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study.

<b>RESULTSb>The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12).

<b>CONCLUSIONSb>Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.

Aged ; Antiviral Agents ; therapeutic use ; Bortezomib ; therapeutic use ; DNA, Viral ; drug effects ; genetics ; Female ; Hepatitis B ; drug therapy ; virology ; Hepatitis B virus ; drug effects ; pathogenicity ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; virology ; Retrospective Studies ; Viral Load