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.

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.

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.

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 carrimycin in ten patients with severe pneumonia following solid organ transplantation

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually.However,infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants.Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene(ist)from streptomyces thermotoleran.Carrimycin has good antibacterial and antiviral effects.However,no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia(SP)after solid organ transplantation.AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment.METHODS In March 2022,ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022.When the condition was critical and difficult to control with other drugs,carrimycin was administered.These ten patients'clinical features and treatment protocols were retrospectively analyzed,and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated.RESULTS All ten patients were included in the analysis.Regarding etiological agent detection,there were three cases of fungal pneumonia,two cases of bacterial pneumonia,two cases of Pneumocystis pneumonia,and three cases of mixed infections.After treatment with carrimycin,the disease in seven patients significantly improved,the course of the disease was significantly shortened,fever was quickly controlled,chest computed tomography was significantly improved,and oxygenation was significantly improved.Finally,the patients were discharged after curing.One patient died of acute respiratory distress syndrome,and two patients discontinued treatment.CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation.Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

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.

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.

Immunopathogenesis of chronic hepatitis B

Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge experimental approaches have demonstrated key pathways that involve cross-talk between viral particles and host immune cells. All events, including penetration of hepatitis B virus (HBV) particles into host cells, establishing persistence, and chronization of CHB infection, and possibility of complete elimination of HBV particles are controlled by the immune system. Researchers have paid special attention to the replication capacity of HBV in host cells, which is associated with cellular changes that reflect presentation of viral antigens and variability of HBV antigen features. In addition, specific HBV proteins have an immune-modulating ability to initiate molecular mechanisms that &#x0201c;avoid&#x0201d; control by the immune system. The relationship between immunological shifts and chronic infection stages has been intensively studied since it was recognized that the immune system is a direct participant in the recurrent (cyclic) nature of CHB. Understanding the wide diversity of molecular pathways and the crosstalk between innate and adaptive immune system components will provide fresh insight into CHB immune pathogenesis and the possibilities of developing new treatment strategies for this disease.

Current therapeutic strategies for recurrent hepatitis B virus infection after liver transplantation

Hepatitis B virus (HBV)-related liver disease is the leading indication for liver transplantation (LT) in Asia,especially in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral antiviral drugs,the recurrent HBV infection rate after LT has been evidently reduced.However,complete eradication of recurrent HBV infection after LT is almost impossible.Recurrent graft infection may lead to rapid disease progression and is a frequent cause of death within the fi rst year after LT.At present,the availability of new oral medications,especially nucleoside or nucleotide analogues such as adefovir dipivoxil,entecavir and tenofovir disoproxil fumarate,further strengthens our ability to treat recurrent HBV infection after LT.Moreover,since combined treatment with HBIG and antiviral agents after liver re-transplantation may play an important role in improving the prognosis of recurrent HBV infection,irreversible graft dysfunction secondary to recurrent HBV infection in spite of oral medications should no longer be considered an absolute contraindication for liver re-transplantation.Published reviews focusing on the therapeutic strategies for recurrent HBV infection after LT are very limited.In this article,the current therapeutic strategies for recurrent HBV infection after LT and evolving new trends are reviewed to guide clinical doctors to choose an optimal treatment plan in different clinical settings.

Novel approaches towards conquering hepatitis B virus infection

Currently approved treatments for hepatitis B virus （HBV） infection include the immunomodulatory agent, IFN-α, and nucleos（t）ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B （CriB） infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed.

Health care-associated hepatitis C virus infection

Hepatitis C virus(HCV)is a blood-borne pathogen that has a worldwide distribution and infects millions of people.Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health.The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified:(1)infected patient to non-infected patient;(2)infected patient to non-infected health careworker(HCW);and(3)infected HCW to non infected patient.For each condition,the circumstances of contamination are described together with the means to prevent them.As a whole,the more important risk is represented by unsafe practices regarding injections,notably with the improper use of multidose vials used for multiple patients.The questions of occupational exposures and infected HCWs are also discussed.In terms of prevention and surveillance,the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares,with training programs and audits to verify their good application.HCWs must be sensitized to the risk of blood-borne pathogens,notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures.The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay.With the need to stay vigilant because HCV infection is often a hidden risk,it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years.

Hepatitis C virus-associated B cell non-Hodgkin's lymphoma

The hepatitis C virus (HCV) infected patients are prone to develop bone marrow or various tissue infiltrates with monoclonal B cells, monoclonal B lymphocytosis or different types of B cell non-Hodgkin&#x02019;s lymphoma (BCNHL), of which the most common are splenic marginal zone BCNHL, diffuse large BCNHL and follicular lymphoma. The association between chronic HCV infection and non Hodgkin&#x02019;s lymphoma has been observed especially in areas with high prevalence of this viral infection. Outside the limitations of some studies that have been conducted, there are also geographic, environmental, and genetic factors that contribute to the epidemiological differences. Various microenvironmental signals, such as cytokines, viral antigenic external stimulation of lymphocyte receptors by HCV antigens, and intercellular interactions contribute to B cell proliferation. HCV lymphotropism and chronic antigenic stimulation are involved in B-lymphocyte expansion, as mixted cryoglobulinemia or monoclonal gammopathy of undetermined significance, which can progress to BCNHL. HCV replication in B lymphocytes has oncogenic effect mediated by intracellular HCV proteins. It is also involved in an important induction of reactive oxygen species that can lead to permanent B lymphocyte damage, as DNA mutations, after binding to surface B-cell receptors. Post-transplant lymphoproliferative disorder could appear and it has a multiclonal potentiality that may develop into different types of lymphomas. The hematopoietic stem cell transplant made for lymphoma in HCV-infected patients can increase the risk of earlier progression to liver fibrosis and cirrhosis. HCV infected patients with indolent BCNHL who receive antiviral therapy can be potentially cured. Viral clearance was related to lymphoma response, fact that highlights the probable involvement of HCV in lymphomagenesis. Direct acting antiviral drugs could be a solution for the patients who did not tolerate or respond to interferon, as they seem to be safe and highly effective. The use of chemotherapy in combination with rituximab for the treatment of BCNHL in patients infected with HCV can produce liver dysfunction. The addition of immunotherapy with rituximab can increase the viral replication, and severe complications can occure especially in patients co-infected with hepatitis B virus or immune immunodeficiency virus, in those with hepatocarcinoma, cirrhosis, or liver cytolysis. But the final result of standard immunochemotherapy applied to diffuse large BCNHL patients with HCV infection is not notably worse than in those without this viral infection. The treatment of patients chronically infected with HCV and having BCNHL is complex and requires a multidisciplinary approach and the risk / benefit ratio of rituximab treatment must be evaluated especially in those with liver cytolysis.

Current trends in management of hepatitis B virus reactivation in the biologic therapy era

Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk ofHBV reactivation is heightened by the use monoclonalantibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and longlasting immunosuppression. Emerging data indicatethat HBV reactivation could also develop following theuse of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is di-agnosed, it is mandatory to suspend biologic treatmentand start antiviral agents immediately. However, preemptive antiviral therapy prior to monoclonal antibodyadministration is crucial in preventing HBV reactivationand its clinical consequences. Several lines of evidencehave shown that risk of HBV reactivation is greatlyreduced by the identifi cation of high-risk patients andthe use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.

Current status of COVID-19 treatment:An opinion review

The pandemic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development.Several drugs have been used for the management of coronavirus disease 2019(COVID-19),which has affected many hospitals and health centers worldwide.Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality,as there are very few published randomized clinical trials.Despite this,the literature offers some material for study and reflection.This opinion review attempts to address three burning questions on COVID-19 treatment options.(1)What kind of studies are currently published or ongoing in the treatment of patients with COVID-19?(2)What drugs are currently described in the literature as options of treatment for patients affected by the infection?And(3)Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy?By answering these questions,we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo,and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.

Potential herb-drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread worldwide.Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence,hospitalization,and mortality.At present,antiviral drugs including Nirmatrelvir/Ritonavir(Paxlovid^(TM)),Remdesivir,and Molnupiravir have been authorized to treat COVID-19 and become more globally available.On the other hand,traditional Chinese medicine(TCM)has been used for the treatment of epidemic diseases for a long history.Currently,various TCM formulae against COVID-19 such as Qingfei Paidu decoction,Xuanfei Baidu granule,Huashi Baidu granule,Jinhua Qinggan granule,Lianhua Qingwen capsule,and Xuebijing injection have been widely used in clinical practice in China,which may cause potential herb-drug interactions(HDIs)in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines.However,information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking,and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19,and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters.These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.

ASFV transcription reporter screening system identifies ailanthone as a broad antiviral compound

African swine fever(ASF)is an acute,highly contagious and deadly viral disease in swine that jeopardizes the worldwide pig industry.Unfortunately,there are no authoritative vaccine and antiviral drug available for ASF control.African swine fever virus(ASFV)is the etiological agent of ASF.Among the ASFV proteins,p72 is the most abundant component in the virions and thus a potential target for anti-ASFV drug design.Here,we con-structed a luciferase reporter system driven by the promoter of p72,which is transcribed by the co-transfected ASFV RNA polymerase complex.Using this system,we screened over 3200 natural product compounds and obtained three potent candidates against ASFV.We further evaluated the anti-ASFV effects and proved that among the three candidates,ailanthone(AIL)inhibits the replication of ASFV at the nanomolar concentration(IC_(50)=15 nmol/L).Our in vitro experiments indicated that the antiviral effect of AIL is associated with its inhibition of the HSP90-p23 cochaperone.Finally,we showed the antiviral activity of AIL on Zika virus and hepatitis B virus(HBV),which supports that AIL is a potential broad-spectrum antiviral agent.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C:Data from the Polish EpiTer-2 cohort study

BACKGROUND The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C,making it highly effective and safe for patients.However,few researchers have analyzed the factors causing therapy failure in some patients.AIM To analyze factors influencing the failure of direct antiviral drugs in the large,multicenter EpiTer-2 cohort in a real-world setting.METHODS The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020.Data collected from the online EpiTer-2 database included the following:hepatitis C virus(HCV)genotype,stage of fibrosis,hematology and liver function parameters,Child-Turcotte-Pugh and Model for End-stage Liver Disease scores,prior antiviral therapy,concomitant diseases,and drugs used in relation to hepatitis B virus(HBV)and/or human immunodeficiency virus(HIV)coinfections.Adverse events observed during the treatment and follow-up period were reported.Both standard and machine learning methods were used for statistical analysis.RESULTS During analysis,12614 patients with chronic hepatitis C were registered,of which 11938(mean age:52 years)had available sustained virologic response(SVR)data[11629(97%)achieved SVR and 309(3%)did not].Most patients(78.1%)were infected with HCV genotype 1b.Liver cirrhosis was diagnosed in 2974 patients,while advanced fibrosis(F3)was diagnosed in 1717 patients.We included patients with features of hepatic failure at baseline[ascites in 142(1.2%)and encephalopathy in 68(0.6%)patients].The most important host factors negatively influencing treatment efficacy were liver cirrhosis,clinical and laboratory features of liver failure,history of hepatocellular carcinoma,and higher body mass index.Among viral factors,genotype 3 and viral load also exerted an influence on treatment efficacy.Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex,which was not confirmed by the multivariate analysis using the machine learning algorithm(random forest).Coinfection with HBV(including patients with on-treatment reactivation of HBV infection)or HIV,extrahepatic manifestations,and renal failure did not significantly affect the treatment efficacy.CONCLUSION In patients with advanced liver disease,individualized therapy(testing for resistance-associated variants and response-guided treatment)should be considered to maximize the chance of achieving SVR.

Favipiravir:a promising investigational agent in preventing infection and progression of COVID-19

In late Dec.2019,a huge number of pneumonia cases caused by novel coronavirus were reported in China.2019-nCoV pandemic has influenced on millions of people's life across the world.This novel coronavirus was identified to be similar with MERS and SARS.Therefore,researchers and academicians across the world still trying to find out vaccines,new drug molecules against SARS-CoV-2.The principle point of this review article is to explain the activity of favipiravir in preventing COVID-19.In view of constrained data available in the literature,we specify that favipiravir treatment,among all other anti-viral drugs,accompanied by oxygen inhalation therapy,maintaining fluid and electrolyte balance,and nutritional support may be helpful in fighting COVID-19.Researches were done on already approved existing anti-viral drugs for treating ebola virus,influenza virus infection and many such anti-viral agents like favipiravir,ritonavir,remdesivir,ribavirin,oseltamivir shows promising results in preventing COVID-19 infection and their clinical trials are currently undergoing in order to discover proper treatment of COVID-19.Among the aforementioned drug candidates,a broad-spectrum RNA polymerase inhibitor favipiravir,which demonstrated a promising tolerance profile and anti-viral efficacy in patients having COVID-19 manifestations.

Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir(WV116)

The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection.So far,a few small-molecule antiviral drugs,including nirmatrelvir-ritonavir(Paxlovid),remdesivir,and molnupiravir have been marketed for the treatment of COVID-19.Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19.However,the existing treatment options have limitations,and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed.To date,four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China.These drugs include azvudine,simnotrelvir-ritonavir(Xiannuoxin),leritrelvir,and mindeudesivir(VV11).Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression.In this review,we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19.These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.

Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis

AIM: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBVGN) patients. METHODS: A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearanceof HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN. RESULTS: Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No signif icant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27]. CONCLUSION: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBVGN patients without altering HBV replication or damaging liver and renal functions.