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.

Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era

To the Editor:Hepatocellular carcinoma (HCC) is the most common primary livertumorandthethirdcauseofcancer-relateddeathsworldwide. HCC is the consequence of malignant transformation of hepatocytes and mainly occurs in patients with cirrhosis. Hepatitis C virus (HCV) chronic infection is a leading cause of end-stage liver diseaseandHCCintheWesterncountries[1].Theapprovalof direct-acting antiviral agents (DAAs) for the treatment of HCV has revolutionized the management of the disease, as no absolute contraindication to treatment exists and sustained virological response

Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-na（i）ve Patients Infected with Genotype 1b Hepatitis C Virus

Background：It has been reported that several baseline polymorphisms of direct-acting antivirals （DAAs） agents resistance-associated variants （RAVs） would affect the treatment outcomes of patients chronically infected with hepatitis C virus （CHC）.The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-na（i）ve GT1b CHC patients.Methods：Direct sequencing and ultra-deep sequencing of the HCV NS3,NS5A,and NS5B gene were performed in baseline serum samples of treatment-ha（i）ve patients infected with genotype lb hepatitis C virus （HCVs）.Results：One hundred and sixty CHC patients were studied.Complete sequence information was obtained for 145 patients （NS3）,148 patients （NS5A）,and 137 patients （NS5B）.Treatment-failure associated variants of DAAs were detected：56.6％ （82/145） of the patients presented S122G for simeprevir （NS3 protease inhibitor）;10.1％ （14/148） of the patients presented Y93H for daclatasvir and ledipasvir （NS5A protein inhibitors）;94.2％ （129/137） of the patients presented C316N for sofosbuvir （NS5B polymerase inhibitor）.Nearly,all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing.Conclusions：The majority of genotype lb CHC patients in China present a virus population carrying HCV DAAs RAVs.Pretreatment sequencing of HCV genome might need to be performed when patients infected with GTlb HCV receiving DAAs-containing regimens in China.Population sequencing would be quite quantified for the work.

Review of Clinically Relevant Drug Interactions with Next Generation Hepatitis C Direct-acting Antiviral Agents

In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(Maviret®),and elbasvir/grazoprevir(Zepatier®).We searched MEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,Maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,2020.The search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference proceedings.All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted.Numerous clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed drugs.NS3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase inhibitor.The majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do occur.As expected,many drug interactions exist between newer generation DAAs and commonly prescribed medications.While the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting drugs.In select cases,severe and unpredictable drug interactions can occur.Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.

DUCK HEPATITIS B VIRUS MODEL FOR SCREENING OF ANTIVIRAL AGENTS FROM MEDICINAL HERBS

The effects of the extracts of 20 Chinese medicinal herbs and an antiviral drug foscarnet on duck hepatitis B virus (DHBV) endogenous DNA polymerase (DNAp) activity were compared. The extracts of P. urinaria showed a dose-dependent inhibition on DHBV DNAp. And those of other herbs showed little inhibition effect. Primary duck hepatocyte (PDH) cultures were used for evaluating effects of the extract of P. urinaria, foscarnet and acyclovir (ACV) on DHBV, and all the drugs or the extracts showed inhibition of DHBV DNA replication. Furthermore, in vivo trials were carried out. Peking ducks infected with LJ-76 strain of DHBV were treated with the extract of P. urinaria or ACV and compared with placebo treated control ducks. The treatment results in the loss or reduction of circulating viral DHBV DNA and DHBsAg.

Response rates to direct antiviral agents among hepatitis C virus infected patients who develop hepatocellular carcinoma following direct antiviral agents treatment

Aim:Patients with chronic hepatitis C virus(HCV)infection who develop hepatocellular carcinoma(HCC)soon after treatment with direct antiviral agents(DAA)may have been harboring hitherto hidden tumors.If this were true,they should have a lower sustained viral response(SVR)rate,since active HCC hampers DAA efficacy.We aimed to verify this hypothesis.Methods:We included all patients who attended an HCV clinic,provided that they:(1)had no previous history of HCC;(2)had received at least one DAA dose;and(3)had been followed-up clinically and ultrasonographically for at least six months after concluding DAA.Results:The study population included n=789 patients(55%males,median age 62 years).A median of 9.3 months(8.8-11.9)after concluding DAA,n=19(2.4%)patients were discovered to harbor HCC.In comparison to all others,patients with HCC were more commonly male(84%vs.54%,P=0.009),obese(47%vs.17%,P=0.002),and cirrhotic(95%vs.35%,P<0.001)and had less commonly achieved an SVR(68%vs.98%,P<0.001).Moreover,they had a trend for being less commonly treatment na?ve(58%vs.67%,P=0.051).Based on multivariate analysis, ;the independent predictors of HCC were male sex(P=0.031),cirrhosis(P=0.004),obesity(P=0.006),and failure to achieve an SVR(P<0.001).Conclusion:Lack of achieving SVR is a strong independent predictor of development of HCC early after treatment of hepatitis C with DAA.Treatment failure should further alert clinicians to the possibility of this dreadful complication.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Global trends in hepatitis C-related hepatocellular carcinoma mortality:A public database analysis(1999-2019)

BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma(HCC).However,there are marked variations in the incidence and mortality rates of HCC across different geographical regions.With the advent of new widely available treatment modalities,such as direct-acting antivirals,it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C.Furthermore,gender disparities in HCC mortality related to Hepatitis C are a crucial,yet underexplored aspect that adds to the disease's global impact.While some studies shed light on gender-specific trends,there is a lack of comprehensive data on global and regional mortality rates,particularly those highlighting gender disparities.This gap in knowledge hinders the development of targeted interventions and resource allocation strategies.DISCUSSION The results of our study show an overall decline in the mortality rates of patients with hepatitis C-related HCC over the last two decades.Notably,females exhibited a remarkable decrease in mortality compared to males.Regionally,East Asia and the Pacific displayed a significant decline in mortality,while Europe and Central Asia witnessed an upward trend.Latin America and the Caribbean also experienced an increase in mortality rates.However,no significant difference was observed in the Middle East and North Africa.North America exhibited a notable upward trend.South Asia and Sub-Saharan Africa significantly declined throughout the study period.This raises the hope of identifying areas for implementing more targeted resources.Despite some progress,multiple challenges remain in meeting the WHO 2030 goal of eliminating viral hepatitis[24].

M2BPGi for assessing liver fibrosis in patients with hepatitis C treated with direct-acting antivirals

BACKGROUND Assessing liver fibrosis is important for predicting the efficacy of direct-acting antivirals(DAAs)and patient prognosis.Non-invasive techniques to assess liver fibrosis are becoming important.Recently,serum Mac-2 binding protein glycosylation isomer(M2BPGi)was identified as a non-invasive marker of liver fibrosis.AIM To investigate the diagnostic accuracy of M2BPGi in assessing liver fibrosis in patients with chronic hepatitis C(CHC)treated with DAAs.METHODS From December 2017 to August 2018,80 treatment-naive adult patients with CHC who were eligible for DAAs therapy were consecutively enrolled in this observational cohort study.For 12 weeks,65 patients were treated with sofosbuvir/daclatasvir,and 15 patients were treated with sofosbuvir/daclatasvir and a weight-based dose of ribavirin at knowledge and technology association for hepatitis C management clinic,Cairo,Egypt.We measured serum M2BPGi levels,PAPAS index,fibrosis-4(FIB-4)score and liver stiffness measurements(LSM)at baseline and 12 weeks after the end of treatment.Serum M2BPGi levels were measured using enzyme-linked immunosorbent assay.RESULTS All patients achieved sustained virologic response(SVR12)(100%).Serum M2BPGi levels,LSM,FIB-4 score and PAPAS index decreased significantly at SVR12(P<0.05).Serum M2BPGi levels correlated positively with LSM at baseline and SVR12(P<0.001).At baseline,compared with the FIB-4 score and PAPAS index,M2BPGi was the best marker to distinguish patients with grade F4 fibrosis(AUC=0.801,P<0.001),patients with grade F2 from grade F0-1 fibrosis(AUC=0.713,P=0.012),patients with grade F3-4 from grade F0-2 fibrosis(AUC=0.730,P<0.001),and patients with grade F2-4 from grade F0-1 fibrosis(AUC=0.763,P<0.001).At SVR12,M2BPGi had the greatest AUCs for differentiating patients with grade F4 fibrosis(AUC=0.844,P<0.001),patients with grade F3 from grade F0-2 fibrosis(AUC=0.893,P=0.002),patients with grade F3-4 from grade F0-2 fibrosis(AUC=0.891,P<0.001),and patients with grade F2-4 from grade F0-1 fibrosis(AUC=0.750,P<0.001).CONCLUSION M2BPGi is a reliable marker for the non-invasive assessment and prediction of liver fibrosis regression in patients with CHC who achieved an SVR with DAAs therapy.

Histopathology and the predominantly progressive,indeterminate and predominately regressive score in hepatitis C virus patients after direct-acting antivirals therapy

BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-I-R)score,evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIM To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODS Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.Sustained virologic response(SVR)was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation.The Ishak system and P-I-R score were assessed.Inflammation improvement and fibrosis regression were defined as a≥2-points decrease in the histology activity index(HAI)score and a≥1-point decrease in the Ishak fibrosis score,respectively.Fibrosis progression was defined as a≥1-point increase in the Ishak fibrosis score.Histologic improvement was defined as a≥2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy.The P-I-R score was also assessed.“absolutely reversing or advancing”was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score;and“probably reversing or advancing”was defined as only one parameter showing directionality.RESULTS Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.The mean age of these patients was 40.9±14.6 years and there were 53%(20/38)males.Thirty-four percent(13/38)of patients were cirrhotic.Eighty-two percent(31/38)of patients achieved inflammation improvement.The median HAI score decreased significantly after SVR(pretreatment 7.0 vs posttreatment 2.0,Z=-5.146,P=0.000).Thirty-seven percent(14/38)of patients achieved fibrosis improvement.The median Ishak score decreased significantly after SVR(pretreatment 4.0 vs posttreatment 3.0,Z=-2.354,P=0.019).Eighty-two percent(31/38)of patients showed histological improvement.The P-I-R score was evaluated in 61%(23/38)of patients.The progressive group showed lower platelet(P=0.024)and higher HAI scores(P=0.070)before treatment.In patients with stable Ishak stage after treatment:Progressive injury was seen in 22%(4/18)of patients,33%(6/18)were classified as indeterminate and regressive changes were seen in 44%(8/18)of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSION Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy.The P-I-R score has potential in predicting fibrosis in HCV patients.

Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals

Chronic inflammation due to hepatitis C virus(HCV)infection leads to liver fibrosis and rearrangement of liver tissue,which is responsible for the development of portal hypertension(PH)and hepatocellular carcinoma(HCC).The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection,providing an overall eradication rate of over 90%.Despite a significant decrease after sustained virological response(SVR),the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease.Although the reasons are still unclear,cirrhosis itself has a residual risk for the development of HCC and other PH-related complications.Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis.Following the achievement of SVR,liver stiffness(LS)usually decreases,as a consequence of reduced inflammation and,possibly,fibrosis.Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease(functional decompensation,gastrointestinal bleeding,HCC)and to optimize long-term prognostic outcomes in clinical practice.

Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil

BACKGROUND Hepatitis C virus(HCV)treatment has undergone major changes in recent years.Previous interferon-based therapies have been replaced by oral direct-acting antivirals(DAA)regimens,with high sustained virologic response(SVR)rates,and a lower incidence of adverse events(AEs).AIM To evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil.METHODS This is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C(CHC),undergoing treatment with interferon-free regimens from November 2015 to November 2019.The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment.Demographic,anthropometric,clinical,and laboratory variables were evaluated.SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat(ITT),and modified ITT(m-ITT)analysis.AEs and serious adverse events(SAEs)were registered.In the statistical analysis,a P value of<0.05 was considered significant.RESULTS The mean age was 56.88 years,with 415(78.5%)being HCV genotype 1,followed by genotype 3(20.1%).Moreover,306(57.5%)subjects had cirrhosis,and a third of them had decompensated cirrhosis.Sofosbuvir(SOF)plus daclatasvir±ribavirin was the most frequently used treatment(66.9%),followed by SOF plus simeprevir(21.2%).The overall ITT SVR was 92.6%(493/532),while the m-ITT SVR was 96.8%(493/509).Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy(OR:4.320;95%CI:1.920-9.721,P=0.0004),presence of esophageal varices(OR:2.381;95%CI:1.137-4.988,P=0.0215),previous portal hypertensive bleeding(OR:2.756;95%CI:1.173-6.471,P=0.02),higher model for end-stage liver disease scores(OR:1.143,95%CI:1.060–1.233,P=0.0005),lower serum albumin levels(OR:0.528,95%CI:0.322-0.867,P=0.0115),higher serum creatinine(OR:1.117,95%CI:1.056-1.312,P=0.0033),and international normalized ratio(INR)levels(OR:5.542,95%CI:2.023-15.182,P=0.0009).AEs were reported in 41.1%(211/514)of patients,and SAEs in 3.7%.The female gender,higher body mass index,esophageal varices,higher INR values,and longer treatment duration were independently associated with AE occurrence.CONCLUSION Treatment with oral DAAs attains a high SVR rate,with fewer SAEs in a real-life cohort of subjects with CHC,from two tertiary university centers in Brazil.

Retreatment of patients with treatment failure of directacting antivirals: Focus on hepatitis C virus genotype 1b

The recent development of direct-acting antiviral agents(DAAs) against hepatitis C virus(HCV) infection could lead to higher sustained virological response(SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions(RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1 b(GT1 b) is founded in 70% of HCVinfected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1 b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1 b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1 b-infected patients with treatment failure.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation.Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver.The expression of these silent genomes is controlled by the immune system.Suppression or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV infection.Thus,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen.Patients found to be positive for HBsAg should be given prophylactic antiviral therapy.For patients with resolved HBV infection,there are two approaches.The first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes detectable.The second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation.Entecavir and tenofovir are the preferred antiviral choices.Many new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV reactivation.Although there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell therapy.Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Past,present,and future of long-term treatment for hepatitis B virus

The estimated world prevalence of hepatitis B virus(HBV)infection is 316 million.HBV infection was identified in 1963 and nowadays is a major cause of cirrhosis and hepatocellular carcinoma(HCC)despite universal vaccination programs,and effective antiviral therapy.Long-term administration of nucleos(t)ide analogues(NA)has been the treatment of choice for chronic hepatitis B during the last decades.The NA has shown a good safety profile and high efficacy in controlling viral replication,improving histology,and decreasing the HCC incidence,decompensation,and mortality.However,the low probability of HBV surface antigen seroclearance made necessary an indefinite treatment.The knowledge,in recent years,about the different phases of the viral cycle,and the new insights into the role of the immune system have yielded an increase in new therapeutic approaches.Consequently,several clinical trials evaluating combinations of new drugs with different mechanisms of action are ongoing with promising results.This integrative literature review aims to assess the knowledge and major advances from the past of hepatitis B,the present of NA treatment and withdrawal,and the future perspectives with combined molecules to achieve a functional cure.

Application of hepatitis B virus replication mouse model

AIM:To evaluate the value of the hepatitis B virus(HBV) replication mouse model with regard to several aspects of the study of HBV biology.METHODS:To evaluate the HBV replication mouse model in detecting the efficacy of anti-HBV agents,the interferon inducer polyinosinic-polytidylin acid(polyIC) and nucleotide analogues adefovir and entecavir were administered to mice injected with wild type pHBV4.1,and the inhibiting effect of these agents on HBV DNA replication was evaluated.To identify the model's value in a replication ability study of HBV drug-resistant mutants and a HBx-minus mutant,telbivudine resistance mutants(rtM204I,ayw subtype),adefovir resistance mutants(rtA181V + rtN236T,ayw subtype) and HBxminus mutants were injected respectively,and their corresponding HBV DNA replication intermediates in mouse liver were assessed.RESULTS:Compared with the wild type HBV replication mouse model without antiviral agent treatment,the HBV DNA replication intermediates of the polyICtreated group were decreased 1-fold;while in the entecavir-and adefovir-treated groups,the levels of HBV DNA replication intermediates were inhibited 13.6-fold and 1.4-fold,respectively.For the mouse models injected with telbivudine resistance mutant,adefovir resistance mutant and HBx-minus mutant,HBV DNA replication intermediates could still be detected,but the levels of HBV DNA replication intermediates of these mutants decreased 4.5-fold,5.6-fold and 2.9-fold respectively,compared with the mouse model with wild type HBV plasmid.CONCLUSION:The HBV replication mouse model we established was a useful and convenient tool to detect the efficacy of antiviral agents and to study the replication ability of HBV mutants in vivo.

Progress and challenges in the comprehensive management of chronic viral hepatitis: Key ways to achieve the elimination

Chronic viral hepatitis is a significant health problem throughout the world,which already represents high annual mortality.By 2040,chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria,vitellogenesis-inhibiting hormone,and tuberculosis altogether.In this review,we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups,the goals set by the World Health Organization for the year 2030,and the key points to achieve them,such as timely access to antiviral treatment of direct-acting antiviral,which represents the key to achieving hepatitis C virus elimination.Likewise,we review the strategies to prevent transmission and achieve control of hepatitis B virus.Finally,we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.

Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease

The prevalence of hepatitis C virus(HCV) infection amongst patients with chronic kidney disease(CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 m L/min per 1.73 m^2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.

Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

AIM: To evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA < 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.

Prediction models for development of hepatocellular carcinoma in chronic hepatitis B patients

Chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC)is a major health problem in Asian-Pacific regions.Antiviral therapy reduces,but does not completely prevent,HCC development.Thus,there is a need for accurate risk prediction to assist prognostication and decisions on the need for antiviral therapy and HCC surveillance.A few risk scores have been developed to predict the occurrence of HCC in CHB patients.Initially,the scores were derived from untreated CHB patients.With the development and extensive clinical application of nucleos(t)ide analog(s)(NA),the number of risk scores based on treated CHB patients has increased gradually.The components included in risk scores may be categorized into host factors and hepatitis B virus factors.Hepatitis activities,hepatitis B virus factors,and even liver fibrosis or cirrhosis are relatively controlled by antiviral therapy.Therefore,variables that are more dynamic during antiviral therapy have since been included in risk scores.However,host factors are more difficult to modify.Most existing scores derived from Asian populations have been confirmed to be accurate in predicting HCC development in CHB patients from Asia,while these scores have not offered excellent predictability in Caucasian patients.These findings support that more relevant variables should be considered to provide individualized predictions that are easily applied to CHB patients of different ethnicities.CHB patients should receive different intensities of HCC surveillance according to their risk category.