Functional cure of chronic hepatitis B-hope or hype?

Chronic hepatitis B constitutes a substantial disease burden worldwide.The steps advocated by the World Health Organization in 2016 to eradicate hepatitis B by 2030 has failed to achieve significant progress,especially with respect to immu-nization coverage and linkage to care.The lack of governmental and public awar-eness regarding the long-term implications of hepatitis B burden cause under-funding of developmental projects.The presently approved treatment modalities have limited efficacy in complete viral eradication,hence the need for newer molecules to achieve functional cure(sustained undetectable hepatitis B surface antigen(HBsAg)and hepatitis B virus DNA in peripheral blood after a finite period of therapy).However,preliminary results from trials of novel therapies show their inadequacy to achieve this end by themselves but better performance with a low baseline serum HBsAg with nucleos(t)ide analogues(NA)treatment which need to be combined with/without pegylated interferon as an immu-nomodulator.Such therapy is limited by cost and adverse events and need to show incremental benefit over the standard of care(long-term NA therapy)with respect to efficacy and drug toxicities,making the development process tenuous.Thus,while such therapies continue to be tested,strategies should still focus on prevention of transmission by non-pharmaceutical measures,vaccination and increasing linkage to care.

Current and future antiviral drug therapies of hepatitis B chronic infection

Despite significant improvement in the management of chronic hepatitis B virus(HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon(IFN)-α and monotherapy with five nucleos(t)ide analogues(NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

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.

Ceftriaxone-induced toxic hepatitis

Toxic hepatitis or drug-induced liver injury encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure.The advantages of a long half-life,wide spectrum,high tissue penetration rate,and a good safety profile,make ceftriaxone,a third-generation cephalosporin,a frequent choice in the treatment of childhood infections.Previous studies have reported a few cases of high aspartate aminotransferase and alanine aminotransferase levels,along with three cases of hepatitis caused by ceftriaxone.Here,we report a case of drug-induced toxic hepatitis in a patient who was treated with ceftriaxone for acute tonsillitis.

Long-term alpha interferon and lamivudine combination therapy in non-responder patients with anti-HBe-positive chronic hepatitis B:Results of an open,controlled trial

AIM: To investigate the safety and efficacy of long-term combination therapy with alpha interferon and lamivudine in non-responsive patients with anti-HBe-positive chronic hepatitis B.METHODS: 34 patients received combination treatment (1 month lamivudine, 12 month lamivudine+interferon, 6month lamivudine), 24 received lamivudine (12 months),24 received interferon (12 months). Interferon was administered at 6 MU tiw and lamivudine at 100 mg orally once daily. Patients were followed up for 6 months after treatment.RESULTS: At the end of treatment, HBV DNA negativity rates were 88 % with lamivudine+interferon, 99 % with lamivudine and 55 % with interferon, (P=0.004, combination therapy vs. interferon, and P=0.001 lamivudine vs.interferon), and serum transaminase normalization rates were 84 %, 91% and 53 % (P=0.01 combination therapy vs. interferon, and P=0.012 lamivudine vs. interferon). Six months later, HBV DNA negativity rates were 44 % with lamivudine+interferon, 33 % with lamivudine and 25 % with interferon, and serum transaminase normalization rates were 61%, 42 % and 45 %, respectively, without statistical significance. No YMDD variants were observed with lamivudine+interferon (vs. 12 % with lamivudine). The combination therapy appeared to be safe. CONCLUSION: Although viral clearance and transaminase normalization are slower with long-term lamivudine+interferon than that with lamivudine alone, the combination regimen seems to provide more lasting benefits and to protect against the appearance of YMDD variants. Studies with other regimens regarding sequence and duration are needed.

Efficacy of 3 years of adefovir monotherapy in chronic hepatitis B patients with lamivudine resistance

AIM: To study the effect of rescue monotherapy with adefovir (ADV) in patients with chronic hepatitis B (CHB) who developed drug resistance to lamivudine (LAM).

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.

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.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Treatment of hepatitis B virus-associated glomerulonephritis:A meta-analysis

AIM:To evaluate the efficacy of antiviral or corticosteroid treatment on hepatitis B virus-associated glomerulonephritis(HBV-GN) . METHODS:Six and five trials were used respectively to evaluate the efficacy of either antiviral or corticosteroid treatment on HBV-GN.Pediatric patients were pooled separately to assess their response to the above treatment modalities.The primary and secondary outcomes were remission of proteinuria and clearance of Hepatitis B e-antigen(HBeAg) ,respectively.A fixed or random effect model was established to collect the data. RESULTS:The remission rate of proteinuria(RR=1.69,95%CI:1.08-2.65) and the clearance rate of HBeAg(RR =6.44,95%CI:3.11-13.35) were significantly higher in antiviral treatment group than in control group.The proteinuria remission was significantly associated with HBeAg clearance(P=0.002) .However,the difference in proteinuria remission rate was not statistically significant between corticosteroid treatment group and controlgroup(RR=1.45,95%CI:0.68-3.11) .Antiviral therapy could significantly promote the HBeAg clearance in pediatric patients,but neither antiviral nor corticosteroid therapy could significantly decrease proteinuria in pediatric patients compared to controls. CONCLUSION:Antiviral but not corticosteroid treatment can decrease proteinuria and promote HBeAg clearance in HBV-GN patients.

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.

Search for a cure for chronic hepatitis B infection: How close are we?

Chronic hepatitis B(CHB) remains a significant unmet medical need, with 240 million chronically infected persons worldwide. It can be controlled effectively with either nucleoside/nucleotide-based or interferonbased therapies. However, most patients receiving these therapies will relapse after treatment withdrawal. During recent years, the advances in molecular biology and immunology have enabled a better understanding of the viral-host interaction and inspired new treatment approaches to achieve either elimination of the virus from the liver or durable immune control of the infection. This review aims to provide a brief overview on the potential new therapies that may overcome the challenge of persistent CHB infection in the near future.

Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis

AIM:Steroids can increase hepatitis C virus(HCV) replication.After liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages.Steroids can worsen the outcome of recurrent HCV infection.Therefore, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS:Thirty patients undergoing LTx received initial steroid-free immunosuppression.Indication for LTx included 7 patients with HCV related cirrhosis.Initial immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMF)2×15mg/kg.d po.The tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L thereafter.Manifestations of acute rejection were verified histologically. RESULTS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years.Acute rejection occurred in 8/30 patients, including 1 HCV infected recipient.All HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after LTx.The virus load was not remarkably increased during the first year after LTx.Histologically,grafts had no severe recurrent hepatitis. CONCLUSION:From our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients.Furthermore,none of the HCV infected patients developed serious chronic liver diseases.It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

Efficacy and cost-effectiveness of antiviral regimens for entecavir-resistant hepatitis B:A systematic review and network meta-analysis

Background:Chronic hepatitis B(CHB)patients who had exposed to lamivudine(LAM)and telbivudine(LdT)had high risk of developing entecavir(ETV)-resistance after long-term treatment.We aimed to conduct a systematic review and a network meta-analysis on the efficacy and cost-effectiveness on antiviral regimens in CHB patients with ETV-resistance.Data sources:We searched PubMed,EMBASE and Web of Science for studies on nucleos(t)ide analogues(NAs)treatment[including tenofovir disoproxil fumarate(TDF)-based rescue therapies,adefovir(ADV)-based rescue therapies and double-dose ETV therapy]in CHB patients with ETV-resistance.The network meta-analysis was conducted for 1-year complete virological response(CVR)and biological response(BR)rates using GeMTC and ADDIS.A cost-effective analysis was conducted to select an economic and effective treatment regimen based on the 1-year CVR rate.Results:A total of 6 studies were finally included in this analysis.The antiviral efficacy was estimated.On network meta-analysis,the 1-year CVR rate in ETV-TDF[odds ratio(OR)=22.30;95%confidence interval(CI):2.78-241.93],LAM-TDF(OR=70.67;95%CI:5.16-1307.45)and TDF(OR=16.90;95%CI:2.28-186.30)groups were significantly higher than that in the ETV double-dose group;the 1-year CVR rate in the LAM-TDF group(OR=14.82;95%CI:1.03-220.31)was significantly higher than that in the LAM/LdTADV group.The 1-year BR rate of ETV-TDF(OR=28.68;95%CI:1.70-1505.08)and TDF(OR=21.79;95%CI:1.43-1070.09)therapies were significantly higher than that of ETV double-dose therapy.TDFbased therapies had the highest possibility to achieve the CVR and BR at 1 year,in which LAM-TDF combined therapy was the most effective regimen.The ratio of cost/effectiveness for 1-year treatment was 8526,17649,20651 Yuan in the TDF group,TDF-ETV group,and ETV-ADV group,respectively.Conclusions:TDF-based combined therapies such as ETV-TDF and LAM-TDF therapies were the first-line treatment if financial condition is allowed.

Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

The proportion of hepatitis B virus(HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation(HBVr) increases with the presence of hepatitis B surface antigen(HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines.

SEN virus does not affect treatment response in hepatitis C virus coinfected patients but SEN virus response depends on SEN virus DNA concentration

AIM: To clarify the effect of SEN virus (SENV) infection on a combination therapy including interferon alfa (IFN-α) or pegylated-IFN with ribavirin in patients with chronic hepatitis and the effect of a combination therapy on SENV.METHODS: SENV DNA was determined by polymerase chain reaction in serum samples from 95 patients with chronic hepatitis C. Quantitative analysis was done for SENV H DNA.RESULTS: Twenty-one (22%) of 95 patients were positive for SENV DNA. There was no difference in clinical and biochemical parameters between patients with HCV infection alone and coinfected patients. The sustained response rate for HCV clearance after combination therapy did not differ between patients with SENV (52%) and without SENV(50%, n.s.). SENV DNA was undetectable in 76% of the initially SENV positive patients at the end of follow-up. SENV H response to combination therapy was significantly correlated with SENV DNA level (P=-0.05).CONCLUSION: SENV infection had no influence on the HCV sustained response rate to the combination therapy.Response rate of SENV to the combination therapy depends on SENV DNA level.

Monitoring hepatitis C virus treatment rates in an Opioid Treatment Program:A longitudinal study

BACKGROUND Direct-acting antivirals(DAAs)are recommended for the treatment of hepatitis C virus(HCV)infection in patients treated with methadone or buprenorphine.AIM To assess HCV treatment rates in an Opioid Treatment Program(OTP).METHODS This longitudinal study included 501 patients(81.4%men,median age:45 years;interquartile range:39-50 years)enrolled in an OTP between October 2015 and September 2017.Patients were followed until September 2019.Data on sociodemographics,substance use,HCV infection,human immunodeficiency virus(HIV)infection and laboratory parameters were collected at entry.We analyzed medical records to evaluate HCV treatment.Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors.RESULTS Prevalence of HCV and HIV infection was 70%and 34%,respectively.Among anti-HCV-positive(n=336)patients,47.2%,41.3%,and 31.9%used alcohol,cannabis,and cocaine,respectively.HCV-RNA tests were positive in 233(69.3%)patients.Twentyeight patients(8.3%)cleared the infection,and 59/308(19.1%)had received interferon-based treatment regimens before 2015.Among 249 patients eligible,111(44.6%)received DAAs.Treatment rates significantly increased over time from 7.8/100 person-years(p-y)(95%CI:5.0-12.3)in 2015 to 18.9/100 p-y(95%CI:11.7-30.3)in 2019.In a multivariate analysis,patients with HIV co-infection were twice as likely to receive DAAs(HR=1.94,95%CI:1.21-3.12)than patients with HCV mono-infection.Current drug use was an independent risk factor for not receiving treatment against infection(HR=0.48,95%CI:0.29-0.80).CONCLUSION HCV treatment is evolving in patients with HCV-HIV co-infection.Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.

Real-world effectiveness of direct-acting antivirals in people living with human immunodeficiency virus and hepatitis C virus genotype 6 infections

BACKGROUND Hepatitis C virus(HCV)genotype 6(HCV-6)infection is prevalent predominantly in Southeast Asia,and the data on the virologic response of HCV-6 to direct-acting antivirals(DAAs)are sparse in people living with human immunodeficiency virus(HIV)(PLWH).AIM To assess the virologic response of HCV-6 to DAAs in PLWH.METHODS From September 2016 to July 2019,PLWH coinfected with HCV-6 initiating DAAs were included.Laboratory investigations were performed at baseline,the end of treatment,and 12 wk off-therapy.RESULTS Of the 349 PLWH included(mean age 48.9 years,82.5%men),80.5%comprised people who inject drugs,18.1%men who have sex with men,and 1.4%heterosexuals.Coexistent hepatitis B virus infection was present in 12.3%of the included PLWH,liver cirrhosis 10.9%,hepatocellular carcinoma 0.9%,and previous HCV treatment experience 10.9%.The mean baseline plasma HCV RNA was 6.2 log10 IU/m L.Treatment with glecaprevir/pibrentasvir was initiated in 51.9%,sofosbuvir/ledipasvir 41.5%,sofosbuvir/velpatasvir 6.3%,and sofosbuvir/daclatasvir 0.3%.At DAA initiation,antiretroviral therapy containing tenofovir alafenamide was given in 26.4%,tenofovir disoproxil fumarate 34.4%,non-tenofovir alafenamide/tenofovir disoproxil fumarate 39.3%,non-nucleoside reverse-transcriptase inhibitors 30.4%,protease inhibitors 4.0%,and integrase strand transfer inhibitors 66.8%;94.8%of the included patients had CD4 counts≥200 cells/mm3 and 96.0%had plasma HIV RNA<50 copies/m L.Overall,96.8%achieved undetectable plasma HCV RNA(<30 IU/m L)at end of treatment;and 92.3%achieved sustained virologic response 12 wk off-therapy in the intention-to-treat analysis(93.5%in patients receiving sofosbuvir-based DAAs and 91.2%in those receiving glecaprevir/pibrentasvir).CONCLUSION Similar to the observation made in HIV-negative patients,sustained virologic response 12 wk offtherapy with DAAs is high in PLWH coinfected with HCV-6.

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.