Natural Products and Antiviral Resistance

Viral diseases are minacious with the potential for causing pandemics and treatment is complicated because of their inherent ability to mutate and become resistant to drugs. Antiviral drug resistance is a persistent problem that needs continuous attention by scientists, medical professionals, and government agencies. To solve the problem, an in-depth understanding of the intricate interplay between causes of antiviral drug resistance and potential new drugs specifically natural products is imperative in the interest and safety of public health. This review delves into natural product as reservoir for antiviral agents with the peculiar potentials for addressing the complexities associated with multi-drug resistant and emerging viral strains. An evaluation of the mechanisms underlying antiviral drug activity, antiviral drug resistance is addressed, with emphasis on production of broad-spectrum antiviral agents from natural sources. There is a need for continued natural product-based research, identification of new species and novel compounds.

Distribution and impacts on the geological environment of antiviral drugs in major waters of Wuhan,China

This study investigated water samples collected from the surface water and groundwater in Wuhan City,Hubei Province,China in different stages of the outbreak of the coronavirus disease 2019(hereinafter referred to as COVID-19)in the city,aiming to determine the distribution characteristics of antiviral drugs in the city’s waters.The results are as follows.The main hydrochemical type of surface water and groundwater in Wuhan was Ca-HCO3.The major chemical components in the groundwater had higher concentrations and spatial variability than those in the surface water.Two antiviral drugs and two glucocorticoids were detected in the surface water,groundwater,and sewage during the COVID-19 outbreak.Among them,chloroquine phosphate and cortisone had higher detection rates of 32.26%and 25.80%,respectively in all samples.The concentrations of residual drugs in East Lake were higher than those in other waters.The main drug detected in the waters in the later stage of the COVID-19 outbreak in Wuhan was chloroquine phosphate,whose detection rates in the surface water and the groundwater were 53.85%and 28.57%,respectively.Moreover,the detection rate and concentration of chloroquine phosphate were higher in East Lake than in Huangjia Lake.The groundwater containing chloroquine phosphate was mainly distributed along the river areas where the groundwater was highly vulnerable.The residual drugs in the surface water and the groundwater had lower concentrations in the late stage of the COVID-19 outbreak than in the middle of the outbreak,and they have not yet caused any negative impacts on the ecological environment.

Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs

Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD). Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons. The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

Character of Frontier Orbitals of Antiviral Drugs: Candidate Drugs against Covid-19

We performed density functional theory (DFT) calculations for ribonucleotides and active triphosphate metabolites of candidate drugs against Coronavirus disease 2019 (Covid-19). Frontier orbitals (highest occupied molecular orbital and lowest unoccupied molecular orbital) at optimized structure of each molecule were obtained. T-705RTP (active triphosphate metabolite of favipiravir) and cytidine triphosphate (CTP) have similar shapes of frontier orbitals. We also obtained similar shapes of frontier orbitals among dihydroxy GS-441524 triphosphate (GS-441524 is an active triphosphate metabolite of remdesivir) and adenosine triphosphate (ATP). From a theoretical viewpoint, we suggest T-705RTP is a CTP analogue and dihydroxy GS-441524 triphosphate is an ATP analogue.

Efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs against recurrent genital herpes:a systematic review and meta-analysis

Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of Science,Cochrane Library,Chinese Biomedical Literature Database,China National Knowledge Internet,VIP Database,and Wanfang Data were searched from inception to April 2021.Randomized controlled trials on the efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs for recurrent genital herpes were collected.All included trials were independently assessed by two reviewers with the Cochrane risk-of-bias tool,and a meta-analysis was conducted using Review Manager 5.4.Results:Compared with the use of nucleoside antiviral drugs alone,combination therapy with oral Chinese herbal medicine plus nucleoside antiviral drugs effectively reduced the herpes recurrence rate after the end of treatment(3 months:P=0.0002;6 months:P<0.00001;1 year:P<0.00001)and the number of recurrences each year(P<0.00001),improved the recurrent Genital Herpes Quality of Life Questionnaire score(P<0.00001),and regulated the levels of interferon-γ,interleukin-2,tumor necrosis factor-α,and T lymphocyte subsets in the peripheral blood,and the difference was statistically significant.Different subgroups reported mixed results with respect to the efficacy in the short term.The incidence of adverse reactions and the time of symptom disappearance between the two groups were not significantly different.Conclusion:Chinese herbal medicine combined with nucleoside antiviral drugs can effectively reduce the recurrence rate of recurrent genital herpes,improve the patient’s quality of life and enhance the body’s immunity.Considering the possible risk of publication bias,more high-quality randomized controlled trials are still needed to verify the conclusions of this article.

Effects of Fuzheng Huayu Capsules combined with nucleoside antiviral drugs on liver and kidney function, serum inflammatory factors, TLR-4, TGF-β1 and aspartate aminotransferase-platelet ratio index in patients with HBV infection and decompensated liver

Objective:To investigate the effect of Fuzheng Huayu Capsule combined with nucleoside antiviral drugs on liver and kidney function,serum inflammatory factors,Toll-like receptor 4(TLR-4),transforming growth factorβ1(TGF-β1)And aspartate aminotransferase-platelet ratio index(APRI).Methods:A total of 144 patients with HBV infection and decompensated cirrhosis were selected.All patients were divided into control group and case group by random number table method,with 72 cases in each group.The control group was given conventional liver protection and antiviral therapy;the case group was supplemented with Fuzheng Huayu Capsule on the basis of treatment in the control group.The changes of liver and kidney function,serum inflammatory factors,TLR-4,TGF-β1 and APRI in the two groups were observed.Results:The total effective rate of the case group was 93.06%,higher than 76.32%of the control group(P<0.05).Case group HBV DNA negative rate,negative rate of hepatitis B virus surface antigen(HBsAg),negative rate of hepatitis B virus e antigen(HBeAg)were significantly higher than the control group(76.39%vs 59.72%,55.56%vs 31.94%,51.39%vs 29.17%),the difference was statistically significant(P<0.05).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),hyaluronic acid(HA),laminin(LN),typeⅢprocollagen after treatment(PCⅢ),typeⅣcollagen(CⅣ),inner diameter of portal vein,inner diameter of splenic vein,spleen thickness,resistance index,urea nitrogen(BUN),creatinine(Cr),interleukin-6(IL-6),interleukin-8(IL-8),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),TLR-4,TGF-β1,APRI are lower than before treatment,albumin(ALB)and renal blood The flow rate was higher than before treatment;liver function indicators,liver fibrosis indicators,liver and spleen imaging indicators,renal hemodynamic indicators,serum inflammatory factors,TLR-4 in the case group The improvement of TGF-β1 and APRI.Conclusion:Fuzheng Huayu Capsules combined with nucleoside antiviral drugs have a clear clinical effect on patients with HBV infection and decompensated liver cirrhosis,significantly improve the clinical symptoms of patients,improve liver and kidney function,reduce inflammatory factor production,and can effectively inhibit HBV replication.Certain promotion value is worthy of further clinical research.

Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection

Objective:To explore the Effects of alprostadil combined with nucleoside antiviral drugs on liver function, liver fibrosis markers and serum inflammatory factors in patients with decompensated liver cirrhosis with HBV infection.Methods: 136 patients with decompensated cirrhosis of HBV infection who were hospitalized in Linxi Hospital of Kailuan General Hospital, Tangshan Infectious Disease Hospital and North China University of Technology Hospital from January to February 2018, 2017 were selected. All patients were divided into control group and case group by random number table method, 68 cases in each group. The control group was treated with routine liver protection and antiviral therapy, while the case group was treated with alprostadil on the basis of the control group. The changes of liver function, liver fibrosis, liver and spleen imaging indexes, anti-virus related indexes and inflammatory factors were observed before and after treatment in the two groups.Results: The total effective rate of the case group was 97.06%, which was significantly higher than that of the control group (85.29%), and the difference was statistically significant. The ALT, AST, TBIL, LN, HA, PCIII, CIV, portal vein diameter, spleen vein diameter, spleen thickness, IL-6, hs-CRP, TNF-α and TGF-β1 were significantly lower in the case group than in the control group. ALB, HBV DNA conversion rate, HBsAg negative rate, and HBeAg negative rate were significantly higher than the control group, the difference was statistically significant. Conclusion: Alprostadil combined with nucleoside antiviral drugs can significantly improve the decompensation of HBV infection Liver function in patients with cirrhosis, reduce the degree of liver fibrosis, inhibit the production of serum inflammatory factors, and can effectively inhibit HBV replication, clinical efficacy is significant, with certain clinical application value.

Expert Consensus on the Clinical Application of Oral Small-molecule Antiviral Drugs Against COVID-19

Although COVID‑19 no longer constitutes a“public health emergency of international concern”,which still has being spreading around the world at a low level.Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China.Although a variety of small‑molecule antiviral drugs against COVID‑19 have been listed in China,there is no specific drug recommendation for special populations.Society of Bacterial Infection and Resistance of Chinese Medical Association,together with the National Clinical Research Center for Respiratory Disease,and the National Center for Respiratory Medicine,organized domestic experts in various fields such as respiratory,virology,infection,critical care,emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small‑Molecule Antiviral Drugs against COVID‑19.The main content of this consensus includes the introduction of seven small‑molecule antiviral drugs against COVID‑19,focusing on the drug recommendations for 14 special groups such as the elderly,patients with complicated chronic diseases,tumor patients,pregnant women,and children,and providing suggestions for clinicians to standardize drug use.

New Method of Palladium Metal Trapping through Resins in Antiviral Drug: Valacyclovir HCl

This process describes a novel technique for effective trapping of “Pd” metal through resins during the process development of L-valine, 2-[(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl) methoxy] ethyl ester, and mono hydrochloride known as a Valacyclovir hydrochloride (1). This technique is suitable for large-scale production of 1 and it is described here Pd metal trapping by using different resins.

Progress in the development and application of plant-based antiviral agents

Plant virus disease is one of the major causes of biological disasters in agriculture worldwide. Given the complexity of transmission media and plant disease infection mechanisms, the prevention and control of plant viral diseases is a great challenge, and an efficient green pesticide is urgently needed. For this reason, when developing candidate drug leads to regulate plant viruses, pesticide experts have focused on characteristics such as low pesticide resistance, eco-friendliness, and novel mechanism. Researchers have also theoretically investigated the molecular targets of viruses infecting agricultural crops. Antiviral screening models have been constructed based on these molecular targets, and the mechanisms of commercial drugs and high-activity compounds have been extensively investigated. After screening, some compounds have been applied in the field and found to have good commercial prospects; these drugs may be used to create new green antiviral pesticides to control plant viruses. This paper reviews the screening, mode of action, development and application of recently used plant-based antiviral agents.

Emerging antivirals for the treatment of hepatitis B

Chronic infection with hepatitis B virus(HBV)constitutes a major global public health threat,causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma,thus representing high unmet medical needs.Currently available therapies are safe,well tolerated,and highly effective in decreasing viremia and improving measured clinical outcomes with low rates of antiviral resistance.However,long-term management remains a clinical challenge,mainly due to the slow kinetics of HBV surface antigen clearance.In this article,we review emerging antivirals directed at novel targets derived from mechanisms of viral cellular entry,viral replication,viral assembly,and the host immune response,leading to preclinical and clinical trials for possible future therapeutic intervention.The recent therapeutic advances in the development of all categories of HBV inhibitors may pave the way for regimens of finite duration that result in long-lasting control of chronic hepatitis B infection.

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents

AIM To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C(CHC) treated with new Direct-Acting Antiviral agents(DAAs) compared to pegylated interferon-2α plus ribavirin(P/R) therapy.METHODS This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus(HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index(PASI) scores and the Dermatology Quality of Life Index(DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different b DMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response(SVR) were considered as outcomes of HCV therapy.RESULTS Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower(P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group(0/27) compared to 8 patients of the P/R group(8/32) needed a shift in biological treatment.CONCLUSION DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis C virus genotypes 1, 2and 3 in northwest China

BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases of special adverse events.One case involved facial and bilateral lower extremity edema,and the other case showed an interesting change in lipid levels while on medication.No severe adverse events were noted.CONCLUSION The DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1,2 and 3,including those with cirrhosis.

Chronic hepatitis B:New potential therapeutic drugs target

liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.

Liver decompensation predicts ribavirin overexposure in hepatitis C virus patients treated with direct-acting antivirals

AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.

Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence:The endless debate

Since direct-acting antiviral agents(DAAs)have been introduced into hepatitis C virus treatment,the sustained viral response(SVR)rate has significantly increased to more than 95%.Scientific evidence supports the idea that SVR after interferon therapy has beneficial effects related to cirrhosis progression,resulting in a reduction in the incidence of hepatocellular carcinoma(HCC).However,a significant debate exists related to DAA impact on HCC development.We reviewed the current literature highlighting the controversial data related to DAA association with de novo HCC occurrence or recurrence and possible pathophysiology of HCC related to DAAs.After a review of the published literature,we believe that the current evidence does not confirm or repudiate a higher rate of de novo HCC occurrence or recurrence related to DAA therapy.More trials are needed to determine if there is an association between HCC occurrence or recurrence and DAA or if it is related to preexisting liver cirrhosis.

Safety of direct acting antiviral treatment for hepatitis C in oncologic setting:A clinical experience and a literature review

With a globally estimated 58 million people affected by,chronic hepatitis C virus(HCV)infection still represents a hard challenge for scientific community.A chronic course can occur among patients with a weak innate ad adaptive response with cirrhosis and malignancies as main consequences.Oncologic patients undergoing chemotherapy represent a special immunocompromised population predisposed to HCV reactivation(HCVr)with undesirable changes in cancer treatment and outcome.Aim of the study highlight the possibility of HCVr in oncologic population eligible to chemotherapy and its threatening consequences on cancer treatment;underline the importance of HCV screening before oncologic therapy and the utility of direct aging antivirals(DAAs).A comprehensive overview of scientific literature has been made.Terms searched in PubMed were:“HCV reactivation in oncologic setting”“HCV screening”,“second generation DAAs”.Pharmacokinetic and Pharmacodynamics characteristics of DAAs are reported,along with drug-drug interactions among chemotherapeutic drug classes regimens and DAAs.Clinical trials conducted among oncologic adults with HCV infection eligible to both chemotherapy and DAAs were analyzed.Viral eradication with DAAs in oncologic patients affected by HCV infection is safe and helps liver recovery,allowing the initiation of cancer treatment no compromising its course and success.

Four FDA-approved drugs exhibited inhibition effect on severe fever with thrombocytopenia syndrome virus in vitro

Objective:To screen the anti-SFTSV drugs from 1430 FDA-approved drugs via mini-genome system,and to investigate which stage of the infection process could be suppressed by the identified drugs.Methods:The SFTSV mini-genome system was used to screen drugs with inhibitory effect on SFTSV replication and transcription,and the 50%inhibitory concentration(IC_(50))of each drug was calculated by drug concentration gradient inhibition experiment.Drugs were used to pre-incubate with virus and then incubate with cells,to incubate with virus and cells simultaneously,to incubate with cells after virus invading into cells,or to incubate during the whole infection process,and then qRT-PCR was used to measure the viral RNA copies in the culture supernatant.These experiments were performed to quantitatively determine the inhibition effects of drugs on SFTSV indifferent stages of the whole process including virion stability,entry and post-entry stages,so as to clarify the inhibition mechanism of these drugs.Results:Four drugs including Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide,and Vidofludimus were identified having efficient inhibitory effects on SFTSV RNA replication via minigenome system,with the IC_(50) of 0.014μmol/L,0.627μmol/L,1.283μmol/L,and 0.059μmol/L,respectively.All four drugs showed effective inhibition when adding during the whole SFTSV infection process as well as the post-entry stage.Conclusion:Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide and Vidofludimus show efficient anti-viral effects on SFTSV infection.

四种抗新型冠状病毒药物对肝功能影响的临床观察

目的 观察阿兹夫定、奈玛特韦、莫诺拉韦、先诺特韦对新型冠状病毒感染患者肝功能的影响。方法 回顾性收集196例应用口服小分子抗病毒药物的新型冠状病毒感染患者的临床资料,根据所用药物不同将患者分为阿兹夫定组(92例)、奈玛特韦组(41例)、莫诺拉韦组(42例)、先诺特韦组(21例)。阿兹夫定组接受阿兹夫定治疗,奈玛特韦组接受奈玛特韦/利托那韦治疗,莫诺拉韦组接受莫诺拉韦治疗,先诺特韦组接受先诺特韦/利托那韦治疗。比较四组患者治疗前后肝功能指标水平,分析四组患者治疗后肝功能异常例数及占比,分析四组治疗后肝功能异常患者年龄及基础疾病。结果 阿兹夫定组治疗7 d后的谷丙转氨酶(47.24±13.86)U/L、谷草转氨酶(48.59±16.71)U/L高于治疗前的(38.87±19.14)、(40.18±22.33)U/L(P<0.05),碱性磷酸酶、总胆红素、直接胆红素与治疗前比较,无统计学差异(P>0.05)。奈玛特韦组治疗5 d后的谷丙转氨酶(61.71±27.74)U/L高于治疗前的(44.95±20.55)U/L(P<0.05),谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素与治疗前比较,无统计学差异(P>0.05)。莫诺拉韦组、先诺特韦组治疗5 d后的谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素与治疗前比较,均无统计学差异(P>0.05)。阿兹夫定组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为28例(30.4%)、9例(9.8%)、4例(4.3%)、0、4例(4.3%)。莫诺拉韦组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为7例(16.7%)、7例(16.7%)、1例(2.4%)、1例(2.4%)、1例(2.4%)。奈玛特韦组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为14例(34.1%)、11例(26.8%)、5例(12.2%)、1例(2.4%)、1例(2.4%)。先诺特韦组谷丙转氨酶、谷草转氨酶、碱性磷酸酶、总胆红素、直接胆红素异常分别为4例(19.0%)、2例(9.5%)、0、0、0。四组治疗后肝功能异常患者共63例,其中男44例(69.8%),女19例(30.2%)。年龄23~90岁,平均年龄73.06岁。无基础疾病14例(22.2%),合并高血压31例(49.2%),合并冠状动脉相关疾病16例(25.4%),合并脑血管病15例(23.8%),合并糖尿病11例(17.5%),合并肿瘤5例(7.9%),合并慢性肺疾病4例(6.3%)。结论 对新型冠状病毒感染患者,口服阿兹夫定显著升高谷丙转氨酶和谷草转氨酶,口服奈玛特韦显著升高谷丙转氨酶,口服莫诺拉韦、先诺特韦后肝功能无显著变化。对口服小分子抗病毒药物患者,需要监测肝功能。

直接抗病毒药物治疗失败的慢性丙型肝炎患者临床特点及基因型分析

目的探索直接抗病毒药物(DAA)治疗失败的慢性丙型肝炎(CHC)患者的临床特点及基因型特征。方法选取2021年9月至2022年12月咸阳市第一人民医院DAA治疗失败的患者28例,同时期DAA治疗成功者100例。酶法检测肝功能、PCR-反向杂交法检测HCV基因型、Sanger测序法检测耐药相关替代突变(RAS)片段,分析DAA观察组患者临床特征及基因型特点。结果失败组和有效组HCV RNA>105 IU/mL分别为23例(82.1%)、34例(34.0%),差异有统计学意义(χ^(2)=20.526,P=0.001)。DAA治疗失败组男性患者TBil、DBil分别为14.61(10.98,20.78)μmol/L、4.94(3.08,7.48)μmol/L,均高于女性患者的6.65(4.90,8.40)μmol/L、2.50(1.78,3.07)μmol/L(Z=-2.018和-2.456,均P=0.01)。纳入患者共检测出3种HCV基因型,分别为1b、2a及3b,有26例未测出基因型,失败组HCV 1b、2a及3b基因型分别为11例(39.3%)、6例(21.4%)及5例(17.8%),有效组分别为56例(56.0%)、15例(15.0%)及9例(9.0%)。失败组检测出NS5A和NS5B2种基因片段,但是RAS发生率不同。结论DAA治疗失败者会受性别、病毒载量、基因型以及RAS种类影响。