Design of novel broad-spectrum antiviral nucleoside analogues using natural bases ring-opening strategy.

The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA-dependent RNA polymerase (RdRp) has emerged as a potential target for broad-spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently-used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the "ring-opening" strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad-spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high-throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 µM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 µM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 µM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 µM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with "ring-opening" bases and suggests the "ring-opening" nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open-loop bases to mimic Watson-Crick base pairing better and improve antiviral activity.

Recommendations for the selection of nucleoside analogues as antihuman herpesvirus drugs: a real-world analysis of reported cases from the FDA adverse event reporting system.

OBJECTIVE: The aim of this study is to provide guidance for refining medication protocols, developing alternative strategies, and enhancing protection against herpesvirus infections in personalized clinical settings. METHODS: Adverse drug events (ADEs) data for anti-herpesvirus from the first quarter of 2004 to the fourth quarter of 2022 were collected from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) methods for data mining. RESULTS: A total of 18,591, 24,206, 6,150, and 419 reports of ADEs associated with acyclovir (ACV), valacyclovir (VACV), ganciclovir (GCV), and famciclovir (FCV) were screened and extracted from the FAERS. In this study, the report summarized the high frequency and strong correlation of ADEs for the four drugs at the Preferred Term (PT) level. Additionally, the analysis also identified the relationship between ADEs and factors such as age, gender, and severity of outcome at the System Organ Class (SOC) level. CONCLUSION: The safety reports for the four-nucleoside analogue anti-herpesvirus drugs are diverse and interconnected. Dosing for patients with herpesvirus infections should be tailored to their specific conditions and the potential risk of disease.

Lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs: A versatile drug delivery paradigm.

Integrating lipid conjugation strategies into the design of nucleoside monophosphate and monophosphonate prodrugs is a well-established approach for discovering potential therapeutics. The unique prodrug design endows nucleoside analogues with strong lipophilicity and structures resembling lysoglycerophospholipids, which improve cellular uptake, oral bioavailability and pharmacological activity. In addition, the metabolic stability, pharmacological activity, pharmacokinetic profiles and biodistribution of lipid prodrugs can be finely optimized by adding biostable caps, incorporating transporter-targeted groups, inserting stimulus-responsive bonds, adjusting chain lengths, and applying proper isosteric replacements. This review summarizes recent advances in the structural features and application fields of lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs. This collection provides deep insights into the increasing repertoire of lipid prodrug development strategies and offers design inspirations for medicinal chemists for the development of novel chemotherapeutic agents.

[Study on mechanism of Chinese Yam polysaccharide synergizing nucleoside analogues against hepatitis B virus through p38 MAPK signaling pathway].

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.

Effects of nucleoside analogues, lipophilic prodrugs and elaidic acids on core signaling pathways in cancer cells.

OBJECTIVES: Nucleoside analogs such as gemcitabine (GEM; dFdC) and cytarabine (Ara-C) require nucleoside transporters to enter cells, and deficiency in equilibrative nucleoside transporter 1 (ENT1) can lead to resistance to these drugs. To facilitate transport-independent uptake, prodrugs with a fatty acid chain attached to the 5'-position of the ribose group of gemcitabine or cytarabine were developed (CP-4126 and CP-4055, respectively). As antimetabolites can activate cellular survival pathways, we investigated whether the prodrugs or their side-chains had similar or decreased effects. METHODS: Two cell lines A549 (non-small cell lung cancer) and WiDr (colon cancer cells) were exposed for 2-24hr to IC50 concentrations of GEM, Ara-C, CP-4126, CP4055 and elaidic acid (EA) concentrations corresponding to the CP-4126 and CP-4055 IC50. Cells were harvested and analyzed for proteins in cell survival pathways (p-AKT/AKT, p-ERK/ERK, p-P38/P38, GSK-3ß/pGSK-3ß) by using Western Blotting. RESULTS: All drugs and their derivatives showed time- and cell-line-dependent effects. In A549 cells, GEM, CP-4126 and EA-4126 decreased the p-AKT/AKT ratio at 2 and 24 hr. For the p-ERK/ERK ratio, GEM, EA-4126, Ara-C, CP-4045 and EA-4055 exposure led to an increase after 6 hr in A549 cells. Interestingly, Ara-C, CP-4055 and EA-4055 decreased p-ERK/ERK ratio in WiDr cells after 4 hr. In A549 cells, the p-GSK-3ß/GSK-3ß ratio decreased after exposure to Ara-C and CP-4055 but in WiDr cells increased after 24 hr. In A549 cells treatment with Ara-C, CP-4055 and EA-4126 decreased the p-P38/P38 after 6 hr. CONCLUSIONS: The findings suggest that both parent drugs, prodrugs, and the EA chain influence cell survival and signaling pathways.

Discovery of C-Linked Nucleoside Analogues with Antiviral Activity against SARS-CoV-2.

The recent COVID-19 pandemic underscored the limitations of currently available direct-acting antiviral treatments against acute respiratory RNA-viral infections and stimulated major research initiatives targeting anticoronavirus agents. Two novel nsp5 protease (MPro) inhibitors have been approved, nirmatrelvir and ensitrelvir, along with two existing nucleos(t)ide analogues repurposed as nsp12 polymerase inhibitors, remdesivir and molnupiravir, but a need still exists for therapies with improved potency and systemic exposure with oral dosing, better metabolic stability, and reduced resistance and toxicity risks. Herein, we summarize our research toward identifying nsp12 inhibitors that led to nucleoside analogues 10e and 10n, which showed favorable pan-coronavirus activity in cell-infection screens, were metabolized to active triphosphate nucleotides in cell-incubation studies, and demonstrated target (nsp12) engagement in biochemical assays.

Design, synthesis and biological evaluation of aryloxy thiophosphoramidate triesters of anticancer nucleoside analogues.

Aryloxy phosphoroamidate triesters, known as ProTides, are a class of prodrugs developed to enhance the physicochemical and pharmacological properties of therapeutic nucleosides. This approach has been extensively investigated in the antiviral and anticancer areas leading to three prodrugs on the market and several others in clinical stage. In this article we have prepared the PS analogues of three ProTides that have reached the clinic as anticancer agents. These novel PS ProTides were tested for their capacity in enzymatic activation and for their cytotoxic properties against a panel of solid and liquid tumor cell lines. As expected, the replacement of the PO with a PS bond led to increased metabolic stability albeit concomitant to a decrease in potency. Surprisingly, the intermediate formed after the first activation step of a thiophosphoramidate with carboxypeptidase Y is not the expected PS aminoacyl product but the corresponding PO aminoacyl compound.

N6-methyltubercidin gives sterile cure in a cutaneous Leishmania amazonensis mouse model.

Leishmania is a trypanosomatid parasite that causes skin lesions in its cutaneous form. Current therapies rely on old and expensive drugs, against which the parasites have acquired considerable resistance. Trypanosomatids are unable to synthesize purines relying on salvaging from the host, and nucleoside analogues have emerged as attractive antiparasitic drug candidates. 4-Methyl-7-ß-D-ribofuranosyl-7H-pyrrolo[2,3-d]pyrimidine (CL5564), an analogue of tubercidin in which the amine has been replaced by a methyl group, demonstrates activity against Trypanosoma cruzi and Leishmania infantum. Herein, we investigated its in vitro and in vivo activity against L. amazonensis. CL5564 was 6.5-fold (P = 0.0002) more potent than milteforan™ (ML) against intracellular forms in peritoneal mouse macrophages, and highly selective, while combination with ML gave an additive effect. These results stimulated us to study the activity of CL5564 in mouse model of cutaneous Leishmania infection. BALB/c female and male mice infected by L. amazonensis treated with CL5564 (10 mg kg−1, intralesional route for five days) presented a >93% reduction of paw lesion size likely ML given orally at 40 mg kg−1, while the combination (10 + 40 mg kg−1 of CL5564 and ML, respectively) caused >96% reduction. The qPCR confirmed the suppression of parasite load, but only the combination approach reached 66% of parasitological cure. These results support additional studies with nucleoside derivatives.

Interferon therapy improves survival in patients with hepatitis B virus-related hepatocellular carcinoma after curative surgery: a meta-analysis.

BACKGROUND AND AIM: A novel study found interferon enhanced antitumor activity of anti-PD-1-based immunotherapy and played a crucial role in improving efficacy on HCC, but the opposite results about the efficacy of interferon on HBV-related HCC were obtained from previous clinical studies and meta-analyses. Thus, this meta-analysis aimed to re-evaluate whether interferon could improve survival and reduce recurrence of patients with HBV-related HCC after curative surgery. METHODS: MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science and CNKI were searched for eligible studies from inception to November 2022 and a meta-analysis was done. RESULTS: 10 trials with a total of 2062 subjects were screened. Interferon significantly improved 1-, 2-, 3- and 5-year OS and 1-, 2- and 3-year DFS, and reduced 2-, 3- and 5-year recurrence rates of patients with HBV-related HCC after curative surgery. However, interferon did not improve 8-year OS and 5-year DFS, did not reduce 1-year recurrence rate. CONCLUSIONS: Interferon may significantly reduce recurrence and improve DFS of patients with HBV-related HCC after curative surgery, and finally improve the OS. However, the efficacy advantage may gradually weaken as time goes on. The clinical application of interferon combined with NAs recommended in this meta-analysis is needed to be further studied.

Mitochondrial-mediated apoptosis as a therapeutic target for FNC (2'-deoxy-2'-b-fluoro-4'-azidocytidine)-induced inhibition of Dalton's lymphoma growth and proliferation.

PURPOSE: T-cell lymphomas, refer to a diverse set of lymphomas that originate from T-cells, a type of white blood cell, with limited treatment options. This investigation aimed to assess the efficacy and mechanism of a novel fluorinated nucleoside analogue (FNA), 2'-deoxy-2'-ß-fluoro-4'-azidocytidine (FNC), against T-cell lymphoma using Dalton's lymphoma (DL)-bearing mice as a model. METHODS: Balb/c mice transplanted with the DL tumor model received FNC treatment to study therapeutic efficacy against T-cell lymphoma. Behavioral monitoring, physiological measurements, and various analyses were conducted to evaluate treatment effects for mechanistic investigations. RESULTS: The results of study indicated that FNC prevented DL-altered behavior parameters, weight gain and alteration in organ structure, hematological parameters, and liver enzyme levels. Moreover, FNC treatment restored organ structures, attenuated angiogenesis, reduced DL cell viability and proliferation through apoptosis. The mechanism investigation revealed FNC diminished MMP levels, induced apoptosis through ROS induction, and activated mitochondrial-mediated pathways leading to increase in mean survival time of DL mice. These findings suggest that FNC has potential therapeutic effects in mitigating DL-induced adverse effects. CONCLUSION: FNC represents an efficient and targeted treatment strategy against T-cell lymphoma. FNC's proficient ability to induce apoptosis through ROS generation and MMP reduction makes it a promising candidate for developing newer and more effective anticancer therapies. Continued research could unveil FNC's potential role in designing a better therapeutic approach against NHL.

Elongation of N6-benzyladenosine scaffold via Pd-catalyzed C-C bond formation leads to derivatives with antiflaviviral activity.

Decoration of nucleoside analogues with lipophilic groups often leads to compounds with improved antiviral activity. For example, N6-benzyladenosine derivatives containing elongated lipophilic substituents in the benzyl core efficiently inhibit reproduction of tick-borne encephalitis virus (TBEV), while N6-benzyladenosine itself potently inhibits reproduction of human enterovirus A71 (EV-A71). We have extended a series of N6-benzyladenosine analogues using effective synthetic methods of CC bond formation based on Pd-catalyzed cross-coupling reactions (Sonogashira and Suzuki) in order to study the influence of bulky lipophilic substituents in the N6 position of adenosine on the antiviral activity against flaviviruses, such as TBEV, yellow fever virus (YFV) and West Nile virus (WNV), as well as a panel of enteroviruses including EV-A71, Echovirus 30 (E30), and poliovirus type 2 (PV2). Reproduction of tested flaviviruses appeared to be inhibited by the micromolar concentrations of the compounds, while cytotoxicity in most cases was beyond the detection limit. Time-of-addition studies demonstrated that the hit compounds inhibited the stage of viral RNA synthesis, but not the stages of the viral entry or protein translation. As a result, several new promising antiflaviviral leads have been identified. On the other hand, none of the synthesized compounds inhibited enterovirus reproduction, indicating a possibility of involvement of flavivirus-specific pathways in their mechanism of action.

[Clinical efficiency and safety of riamilovir under various dosage regimens for treatment of acute respiratory viral infections in adults].

AIM: To evaluate the clinical efficacy and safety of antiviral drug riamilovir in patients with acute respiratory viral infections (ARVI) of non-coronavirus (SARS-CoV-2) etiology with different dosing regimens. MATERIALS AND METHODS: The study included 150 patients with ARVI aged 18-27 years (50 patients received riamilovir in the regimen of 250 mg 3 times a day for 5 days, 50 patients received riamilovir in the off label regimen of 250 mg 5 times a day for 5 days, 50 patients received only pathogenetic treatment). RESULTS: The use of riamilovir in both treatment regimens led to a reduction in the duration of inpatient treatment. The shortest periods of hospitalization were noted in patients who received the study drug at higher daily dosages. The use of riamilovir reduced the duration and severity of general infectious manifestations of the disease, while the shortest total duration of fever and a number of respiratory tract syndromes was registered among people who received riamilovir in the regimen of 1250 mg per day for 5 days, no adverse events were registered, additionally, 100% elimination of ARVI pathogens was noted in 1250 mg per day group. CONCLUSION: Riamilovir has shown clinical efficacy and a good safety profile in in both treatment regimens. The dosage regimen of 1250 mg per day led to more significant clinical effects and to 100% elimination of ARVI pathogens in the study group by the 6th day of hospitalization.

Establishment and application of hepatic organoid model of hepatitis B virus infection / 中华传染病杂志

Objective:To establish the hepatic organoid of hepatitis B virus (HBV) infection on the basis of induced pluripotent stem cells (iPSC) and an inverted colloidal crystal polyethylene glycol scaffold (ICC), and to evaluate the antiviral effect of nucleoside drugs.Methods:iPSC was differentiated into hepatocyte-like cells (HLC), and inoculated into ICC to construct a hepatic organoid. The relative mRNA expressions of Nanog homeobox (NANOG), sex determining region Y-box (SOX) 2, SOX17, forkhead box protein A2 (FOXA2), alpha fetoprotein (AFP) and albumin (ALB) were detected by real time quantitative polymerase chain reaction (RT-qPCR). Confocal laser microscopy was used to photograph the three-dimension (3D) structure of organs. The expression of sodium taurocholate cotransporting polypeptide (NTCP) in HLC was analyzed by Western blot and immunofluorescence. HepG2.2.15 cells were used to extract HBV virus particles to infect hepatic organoid. The relative expression of HBV pregenome RNA (pgRNA) in cells was detected by RT-qPCR. The expressions of hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg) in cytoplasm were observed under confocal laser microscopy. A total of 0.5 μmol/L entecavir and 0.5 μmol/L lamivudine were used to treat the infected cells respectively. The relative expression of HBV pgRNA in infected and uninfected cells was detected by RT-qPCR. Independent sample t test and one-way analysis of variance were used for statistical analysis. Results:Within 21 days of iPSC differentiation, the mRNA expressions of NANOG and SOX2 in stem cells markers decreased ( F=158.90 and 8.31, respectivley; P<0.001 and P=0.002, respectively), while the mRNA expressions of SOX17 and FOXA2 in the endoderm increased first and then decreased ( F=37.23 and 82.57, respectively, both P<0.001). In the later stage of differentiation, the mRNA expressions of AFP and ALB in liver cells increased ( F=4.65 and 34.64, respectively, P=0.012 and P<0.001, respectively), and all differences were statistically significant. NTCP was highly expressed in differentiated cells detected by Western blot and fluorescence microscopy, the protein expression level was 0.803±0.099. Confocal laser microscopy confirmed that the differentiated cells expressed ALB and presented spherical structure in ICC. The expression of HBV pgRNA and the immunostaining of HBsAg and HBcAg confirmed that HBV successfully infected hepatic organoid. Three days after the application of entecavir and lamivudine, the HBV pgRNA level decreased significantly both in entecavir group (0.665±0.220) and lamivudine group (0.503±0.117) compared to the uninfected cells (3.347±0.454), and the differences were both statistically significant ( t=10.53 and 12.72, respectively, both P<0.001). Conclusions:HLC display hepatic specific genes ALB and NTCP. Hepatic organoids constructed with iPSC and ICC have human liver function and can be infected by HBV. Entecavir and lamivudine could effectively inhibit the replication of HBV in hepatic organoids.

Progress in treatment of anti-hepatitis B virus drug nucleoside analogues in preventing mother-to-child transmission / 中国药理学通报

Mother-to-child transmission of hepatitis B virus (HBV) is one of the main ways of transmission and the main cause of chronic hepatitis B after infection. Therefore, preventing mother-to-child transmission of HBV is particularly important in reducing the incidence of chronic hepatitis B. Currently, nucleoside ( acid) analoids ( Nas ) used for mother-to-child blocking of HBV include lamivudine (LAM) , tibivudine (LdT) and tenofovir fumarate ( TDF). Propofol tenofovir fumarate (TAF) has also been used in pregnant chronic hepatitis B pa- tients. This paper summarizes the efficacy, safety and antiviral treatment indications and termination time of the above-mentioned drugs in mother-to-child preventing to provide suggestions for the selection and rational application of mother-to-child preventing Nas.

Discontinuation of nucleoside/nucleoside analogues therapy in compensated patients with hepatitis B cirrhosis after HBsAg negative conversion / 中华临床感染病杂志

Objective:To evaluate the safety of discontinuing nucleoside/nucleoside analogue (NAs) therapy in patients with compensated hepatitis B cirrhosis after HBsAg negative conversion.Methods:A total of 3 783 patients with hepatitis B cirrhosis in compensated stage were treated with NAs at Taizhou Hospital, Taizhou Municipal Hospital and Taizhou Enze Hospital from January 2008 to December 2020. The clinical data and laboratory tests results of 85 patients with HBsAg negative conversion were retrospectively analyzed, including 36 cases discontinued the drug, and 49 continued to use drug. Chi-square test and rank-sum test were used for data analysis.Results:During the 24 and 48 months of follow-up, the ALT levels were within the normal range in both groups. There were no significant differences in positive rates of anti-HBs and HBeAg ( χ2=0.75, 0.39 and 0.90, P=0.78 0.84 and 0.34; χ2=0.40, 0.00 and 0.00, P=0.84, 1.00 and 1.00) between two groups. After 48 months of follow-up, 2 cases of primary liver cancer occurred in the discontinuation group and no primary liver cancer occurred in the continuation group ( χ2=0.89, P=0.34). Throughout the follow-up, HBsAg remained negative and HBV DNA load was below the lower limit of detection in both groups. Conclusions:Discontinuation of NAs can be considered after the HBsAg negative conversion in patients with compensated hepatitis B cirrhosis.

Role of the stability of deoxyribonucleoside triphosphate pool in the development and progression of tumors / 肿瘤研究与临床

The stability of deoxyribonucleoside triphosphate (dNTP) pool is essential for the normal synthesis of nuclear and mitochondrial DNA. The lack or excess of any dNTP may cause DNA damage and genomic instability, and increase mutation rate. Present studies have confirmed that the instability of dNTP pool is closely related to a variety of tumorigenesis. In addition, dNTP pool is involved in the development of tumor via multiple pathways, while the mechanisms of tumors caused by the instability of dNTP are complicated. This paper discusses the relationship between the stability of dNTP pool and DNA damage repair to provide a theoretical basis for early diagnosis and targeted treatment of tumors.

High-dose tenofovir is not effective in suppressing hepatitis B virus replication in patients with hepatocellular carcinoma progression: a preliminary result

BACKGROUNDS/AIMS: Nucleos(t)ide analogues (NUCs) effectively suppress hepatitis B virus (HBV) replication, but hepatocellular carcinoma (HCC) recurrence often leads to HBV replication despite NUC therapy. The aim of this study was to determine whether high-dose tenofovir (TNF) therapy can suppresses HCC recurrence-associated HBV replication. METHODS: We performed a single-arm prospective study to assess the clinical feasibility of high-dose TNF (hdTNF). We recruited 10 patients during September 2015 and followed up for 3 months or early drop-out. RESULTS: All 10 patients had HCC of advanced stages due to HCC recurrence and gradual progression. The average age of patients was 51.2+/-4.7 years and 9 were male. Three patients did not tolerate the increased TNF dosage and were dropped out early. The other 7 patients were relatively tolerable to the increased dosage of TNF 5 tablets per day. One patient had mild gastrointestinal symptoms and another patient complained of insomnia. Increased HBV replication and HCC progression was observed despite hdTNF for 4-8 weeks. All 7 patients showed tumor progression during the 3 month follow-up. In these patients, blood HBV DNA before hdTNF was 50-200 copies/ml; and 4-8 weeks after hdTNF, the HBV replication status was not improved with blood HBV DNA of 50-300 copies/ml. This clinical study was terminated early after these negative results were confirmed. CONCLUSIONS: The results of this study indicated that high dose of TNF up to 5-fold the recommended dosage is not tolerated by a considerable proportion of patients and also ineffective in suppressing HCC progression-associated HBV replication.

Efficacy of nucleoside analogues antiviral therapy on clinical outcome for HBV-related primary hepatic carcinoma patients after hepatectomy / 实用医学杂志

Objective To evaluate the efficacy of nucleoside analogues (NAs) antiviral therapy on clinical outcome for hepatitis B virus (HBV)-related primary hepatic carcinoma patients after hepatectomy. Methods The clinical data of 156 HBV-related primary hepatic carcinoma patients after hepatectomy were retrospectively analyzed..According to whether accepted postoperative antiviral treatment, all patients were divided into control group (n = 80)and observation group (n = 76). The serum HBV DNA capacity, recurrence-free survival (RFS)and overall survival (OS)were compared between two groups. Results One week, 1 month, 2 months and 3 months after operation , the serum HBV DNA capacity of observation group was significantly lower than that of control group(P < 0.05). One year, 3 years and 5 years after operation, intergroup comparison of RFS rate of both groups showed statistical significance (P < 0.05) and 1 year, 3 years and 5 years after operation, the difference of OS rate of both groups indicated statistical significance (P < 0.05). Conclusion Standard NAs antiviral treatment for HBV-related primary hepatic carcinoma patients after hepatectomy ,can improve prognosis and prolong survival time. The inhibition the HBV copy active may be its mechanism.

Progress in study of antiviral effect of chronic hepatitis B / 药学实践杂志

Chronic hepatitis B is a worldwide infectious diseases caused by hepatitis B virus (HBV) .HBV infection is an important reason for liver cirrhosis and liver cancer in our country .Currently ,the interferon and nucleoside analogs antiviral drugs (nucleotides) is widely used in clinical practice .These drugs inhibit the replication of the virus and disease development to a certain extent ,but not fundamentally eliminate the virus .Various therapeutic vaccines have also made certain curative effect in anti HBV ,but the effect is not perfect clinically .At present ,many research results demonstrate that biological immu-notherapy can successfully eliminate HBV virus in the body , therefore it has brought a new hope for the treatment of hepatitis B .

Study on the effect of liver function and tumor marker of patients with liver cirrhosis after hepatitis B by nucleoside drugs Entecavir / 中国生化药物杂志

Objective To investigate the effects of liver function and tumor markers by nucleoside analogues Entecavir on patients with liver cirrhosis after hepatitis B.Methods 90 patients with liver cirrhosis after hepatitis B were selected, according to the different drugs were divided into experimental group and control group.Liver function and levels of tumor markers were compared after experiment.Results Two groups of patients with male to female ratio, average age, course of disease, no significant difference in general data of hepatitis B virus DNA content, comparable (P>0.05);Compared with the control group, the experimental group HBV DNA level is low, the negative rate was significantly higher (P<0.05);Compared with the control group, the experimental group ALT, AST and TBiL levels were significantly increased(P<0.05), ChE, AlB were significantly decreased (P<0.05);Compared with the control group, the experimental group CEA, AFP, CA125 and lower CA199 levels (P<0.05).Conclusion Nucleoside drugs can significantly improve liver function in patients with liver cirrhosis after hepatitis Band tumor markers indicators, and it is significance for treatment of liver cirrhosis after hepatitis.