entecavir and Hepatitis-C

To assess the incidence of hepatitis B virus (HBV) reactivation in patients receiving direct-acting antiviral agent (DAA)-based therapy or interferon (IFN)-based therapy for hepatitis C and the effectiveness of preemptive anti-HBV therapy for preventing HBV reactivation.. The PubMed, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAA-based therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model.. The rate of HBV reactivation was 21.1% in hepatitis B surface antigen (HBsAg)-positive patients receiving DAA-based therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBsAg-positive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy (RR = 0.20, 95%CI: 0.06-0.64,. The rate of HBV reactivation and hepatitis flare occurrence is higher in HBsAg-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.

Topics: Antibiotic Prophylaxis; Antiviral Agents; Coinfection; Disease Progression; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C; Humans; Incidence; Interferons; Recurrence; Tenofovir; Treatment Outcome; Virus Activation

Despite the reciprocal inhibition exerted by HBV and HCV genomes, dual HBV/HCV infection is associated with more severe forms of liver disease and warrant effective treatment. Areas covered: A careful evaluation of disease progression to establish the predominance of one virus over another, concomitant HIV infection and comorbidities is essential to make the best therapy choices. In most virological conditions interferon (IFN)-based treatment has been replaced by a combination of different classes of second generation directly acting antivirals (DAAs), which offer better tolerability and HCV eradication in 95% of cases. Tenofovir or entecavir should be part of treatment for patients with active HBV production, for those coinfected with HIV and for those with cirrhosis. Expert opinion: DAAs have been successfully used to eradicate HCV infection in recent years, but the high cost may limit their use particularly in developing countries. Entecavir and tenofovir have been demonstrated to be effective for long-term inhibition of HBV replication. Careful monitoring of serum ALT and markers of HBV and HCV replication before and during treatment is essential for an early diagnosis and treatment of virus reactivation.

Topics: Anti-HIV Agents; Antiviral Agents; Coinfection; Guanine; Hepatitis C; HIV Infections; Humans; Tenofovir

In patients with lymphoma the detection of positive hepatitis B or C viruses (HBV and HCV) serology involves crucial therapeutic consequences. In HBV-infected patients the serological profile of active (HBsAg-positive) or resolved (HBsAg-negative/anti-HBcAb-positive) infection is associated to differential risk of viral reactivation during rituximab-based therapy and require appropriate strategies of monitoring and of antiviral prophylaxis. In HCV-associated NHL patients consolidated data demonstrated that interferon (IFN)-based antiviral therapy (AT) is able to induce lymphoma regression strictly related to viral eradication, while preliminary data of the new direct-acting antivirals (DAAs) are very promising. Areas covered: This review summarizes current evidences about HBV reactivation risk in patients undergoing rituximab-based treatments and appropriate options of antiviral prophylaxis with lamivudine, entecavir or tenofovir, as well as pre-emptive strategy in HBsAg-negative/HBcAb-positive patients. Moreover previous experiences with IFN-based AT as well as recent studies with DAAs in HCV-associated indolent lymphomas or diffuse large B-cell lymphoma (DLBCL) are reviewed. Expert opinion: Entecavir or tenofovir prophylaxis is recommended for HBsAg-positive patients, while universal prophilaxis with lamivudine may be preferred in HBsAg-negative/anti-HBc-positive patients. In asymptomatic patients with HCV-associated indolent lymphoma DAA-based AT should be used as first-line option, while in DLBCL its deliver after immunochemotherapy-induced complete remission is suggested.

Topics: Antiviral Agents; Guanine; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis C; Humans; Lamivudine; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Rituximab; Tenofovir; Virus Activation

Patients with chronic hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection are at a high risk of developing liver cirrhosis and hepatocellular carcinoma, and consequently, warrant effective treatment.. Effective treatment should eradicate HCV infection and inhibit HBV replication but without serious adverse reactions. Careful evaluation of disease progression, predominance of one virus over another, comorbidities and concomitant hepatitis delta virus and/or HIV infection are essential for better therapy choices. In the case of HCV predominance, Peg-interferon plus ribavirin with or without a first-generation directly acting antiviral (DAA) should be the first choice, but future treatments will be DAA-based and interferon-free. In the case of HBV predominance, tenofovir or entecavir should be part of treatment. Patients should be closely monitored for early identification and treatment of HCV or HBV reactivation.. High potency and high genetic barrier nucleos(t)ide analogues to inhibit HBV replication have been used for years, with no urgency for new drugs. Several DAAs for interferon-free therapy for HCV eradication will be available in the near future. We hope that the high cost of these drugs will not be a limitation to their use in developing countries. Further investigation of HBV/HCV interaction is needed before and during the administration of new therapies.

Topics: Adenine; Antiviral Agents; Coinfection; DNA, Viral; Drug Therapy, Combination; Guanine; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Hepatitis C, Chronic; HIV Infections; Humans; Organophosphonates; Ribavirin; RNA, Viral; Tenofovir; Virus Replication

HCV-related liver disease is an important contributor to morbidity and mortality in the HIV-infected population. Successful treatment of HIV-HCV-coinfected patients is followed by favourable clinical outcomes. While the combination of pegylated interferon and ribavirin remains the mainstay in the treatment of non-1 HCV genotypes, the first generation of HCV protease inhibitors are being incorporated into existing HCV genotype-1 (HCV-1) treatment protocols. Although data are limited, the triple combination does improve the sustained virological response in HIV-HCV-1-coinfected subjects. However, with still very limited data in this setting, clinical decisions for triple therapy have to be individualized and made based on multiple considerations. Chronic HBV infection increases mortality in HIV-infected subjects. In the treatment of HIV-HBV coinfection, it is very important to coordinate HBV and HIV therapies. HBV-active HAART improves the outcome of patients with HIV-HBV coinfection and tenofovir has become a key component of the treatment for these patients, although a number of clinical situations require a case-by-case approach.

Topics: Adenine; Antiretroviral Therapy, Highly Active; Antiviral Agents; Coinfection; Drug Therapy, Combination; Guanine; Hepatitis C; HIV Infections; Humans; Interferon-alpha; Organophosphonates; Polyethylene Glycols; Protease Inhibitors; Recombinant Proteins; Ribavirin; Tenofovir

The combination of antiretroviral (ARV) therapies introduced at the end of the 1990s profoundly changed the natural history of human immunodeficiency virus (HIV) infection. Liver diseases are one of the three primary causes of 'non-AIDS-related' death in people living with HIV for three reasons: the high prevalence of hepatotropic viral co-infections, the hepatotoxicity of ARV drugs and new emerging liver diseases, including nodular regenerative hyperplasia and hepatitis E virus infection. The impact of HIV infection on the natural history of hepatitis C virus (HCV) or hepatitis B virus (HBV)/HIV co-infection has markedly changed in the past few decades with the progress made in ARV treatment and the improved definition of therapeutic strategies for HCV or HBV. Initially, HIV had a negative impact on hepatotropic infections. Today, HIV does not appear to significantly modify the natural history of HCV and HBV infection. This is associated with fair immune restoration, viral suppression associated with analogues having dual activity against HBV and HIV and with the increasing efficacy of antiviral treatments against HCV. A significant decline is expected in the morbidity and mortality associated with chronic liver infection in co-infected patients. Nevertheless, today, there are three major issues: (i) improving preventive measures including vaccination and risk reduction; (ii) screening patients infected with HBV or HCV and evaluating the impact of chronic infection on the liver and finally; (iii) early screening of hepatocellular carcinoma whose occurrence is higher and that evolves more rapidly in co-infected than in mono-infected patients.

Topics: Adenine; Antiviral Agents; Deoxycytidine; Disease Progression; Drug Therapy, Combination; Emtricitabine; Guanine; Hepatitis B; Hepatitis C; Hepatitis Viruses; HIV Infections; Humans; Interferon-alpha; Lamivudine; Nucleosides; Organophosphonates; Pyrimidinones; Telbivudine; Tenofovir; Thymidine

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M(2) inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.

Topics: Acyclovir; Adenine; Amantadine; Antiviral Agents; Comorbidity; Drug Therapy, Combination; Foscarnet; Ganciclovir; Guanine; Hepatitis; Hepatitis B, Chronic; Hepatitis C; Herpesviridae Infections; HIV Infections; Humans; Influenza, Human; Interferons; Lamivudine; Nucleosides; Oligopeptides; Organophosphonates; Oseltamivir; Proline; Protease Inhibitors; Pyrimidinones; Ribavirin; Telbivudine; Thymidine; Valacyclovir; Valganciclovir; Valine; Virus Replication; Zanamivir

Topics: Adenine; Antiviral Agents; Drug Therapy, Combination; Guanine; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Lamivudine; Mutation; Oligopeptides; Organophosphonates; Proline; Ribavirin; Serine Proteinase Inhibitors

Topics: Adenine; Antiviral Agents; Drug Resistance, Viral; Gene Products, pol; Guanine; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Interferons; Lamivudine; Mutation; Organophosphonates; Ribavirin; Viral Nonstructural Proteins

Treatments for infections with hepatitis B and C viruses have recently developed markedly, and range from nonspecific interferon-based treatments to specific antiviral treatments, such as those that inhibit hepatitis virus-coded protein production or activity. These developments have contributed to the achievement of excellent enhancement of the antiviral effect. On the other hand, the development of specific antiviral therapies has created unprecedented problems. Antiviral drug-resistant strains of viruses have emerged, leading to a poor prognosis for infected patients. Clarification of the mechanisms underlying the emergence of such resistance to drugs will be useful for the treatment of such patients. In this review, we outline pathological conditions associated with hepatitis B and C viruses and their treatments, and discuss the current situation and mechanisms underlying the emergence of antiviral drug-resistant strains.

Topics: Adenine; Antiviral Agents; Drug Resistance, Viral; Guanine; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Lamivudine; Organophosphonates

A strategy to prevent hepatitis B virus (HBV) virologic reactivation (HBVr) and clinical reactivation (CR) during direct acting antiviral (DAA) treatment of hepatitis C virus (HCV)/HBV dual infection remains an unresolved issue.. Noncirrhotic patients with dual HCV/HBV infection were enrolled and allocated randomly to 1 of 3 groups as follows: 12 weeks of DAA alone (group 1), 12 weeks of DAA plus 12 weeks of entecavir (group 2), or 12 weeks of DAA plus 24 weeks of entecavir (group 3). The entire study duration was 72 weeks. The primary end point was the occurrence of HBVr (defined by an increase of HBV DNA level >10-fold with quantifiable HBV DNA at baseline or the presence of HBV DNA with prior unquantifiable HBV DNA) and CR (defined by serum alanine aminotransferase level >2-fold the upper limit of normal in addition to HBVr).. Fifty-six patients were allocated randomly as follows: 20 patients in group 1, 16 patients in group 2, and 20 patients in group 3. In group 1, HBV DNA levels increased significantly as early as 4 weeks after initiation of DAA and persisted until the end of the study. During DAA treatment, HBVr occurred in 50% in group 1 vs 0% in group 2 and 0% in group 3 (P < .001), whereas the majority of HBVr in groups 2 and 3 occurred 12 weeks after cessation of entecavir (cumulative incidence, 93.8% in group 2 and 94.7% in group 3). Three patients (5.4%; 1 in each group) showed CR at week 48 and did not receive entecavir treatment.. Twelve weeks of entecavir is suggested to be co-administered with DAA for HCV/HBV dually infected patients.. gov no: NCT04405011.

Topics: Antiviral Agents; DNA, Viral; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Hepatitis C, Chronic; Humans; Virus Activation

The objectives of this study were to determine how HCV infection affects placental drug transporters, and to determine the role of drug transporters on the cellular accumulation of direct-acting antiviral drugs in human trophoblasts.. Eighty-four ABC and SLC transporter genes were first screened in normal and HCV infected pregnant women using PCR profiler array. The changes in expression were confirmed by qPCR and Western blot. The impact of selected drug transporters on the cellular accumulation of radiolabeled antiviral drugs sofosbuvir, entecavir, and tenofovir was measured in primary human trophoblasts (PHT) and BeWo b30 cells in the presence or absence of transporter-specific inhibitors. PHT were then treated with CL097, ssRNA40, and imquimod to determine the impact of Toll-like receptor (TLR) 7/8 activation on drug transporter expression.. The expression of the ABC efflux transporters ABCB1/P-gp and ABCG2/BCRP was increased in placenta of women with HCV, while the nucleoside transporters SLC29A1/ENT1 and SLC29A2/ENT2 remained unchanged. The accumulation of sofosbuvir and tenofovir was unaffected by inhibition of these transporters in trophoblast cells. Entecavir accumulation was decreased by the inhibition of ENT2. P-gp and BCRP inhibition enhanced entecavir accumulation in BeWo b30, but not PHT. Overall, there was little effect of TLR7/8 activation on these drug transporters, and the accumulation of entecavir in PHT.. The data suggest that expression of placental drug transporters and selection of antiviral drug may impact fetal drug exposure in pregnancies complicated by HCV infections.

Topics: Antiviral Agents; ATP-Binding Cassette Transporters; Biological Transport; Female; Guanine; Hepatitis C; Humans; Placenta; Pregnancy; Sofosbuvir; Solute Carrier Proteins; Tenofovir; Trophoblasts

Reactivation of the hepatitis B virus (HBV) has been reported in patients with occult infection (OBI), i.e. HBV surface antigen (HBsAg) negative, HBV core antibody (anti-HBc) positive ± antibodies against HBsAg (anti-HBs) and detectable HBV DNA in serum or liver, receiving immunosuppressive or cytotoxic therapies. Recently, concerns have been raised regarding the risk of HBV reactivation in OBI patients treated with direct acting antiviral agents (DAAs) for chronic hepatitis C (CHC). Here we describe a case of HBV reactivation in a 72-year-old woman with OBI as a possible consequence of effective treatment with sofosbuvir (SOF) and ribavirin (Rbv) for genotype 2a/2c CHC.

Topics: Aged; Anti-Inflammatory Agents; Antiviral Agents; Cryoglobulinemia; DNA, Viral; Female; Guanine; Hepatitis B; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C; Humans; Immunologic Factors; Prednisolone; Recurrence; Ribavirin; Rituximab; Sofosbuvir; Viral Load

Topics: Adenine; Antiviral Agents; Drugs, Essential; Global Health; Guanine; Health Priorities; Hepatitis B; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Organophosphonates; Polyethylene Glycols; Practice Guidelines as Topic; Recombinant Proteins; Tenofovir; World Health Organization

Sixty year-old male positive for both HCV-RNA and HBsAg was treated by triple therapy of peginterferon alpha2b, ribavirin and telaprevir. Eight weeks after the beginning of the therapy, the patient developed drug induced hypersensitivity syndrome (DIHS) with general erythema multiforme and 64 times anti-HHV6 antibody elevation. Sixty milligram of prednisolone was administered with gradual dose reduction and the skin lesion was improved. HBV-DNA and transaminase elevated one week after the steroid induction and entecavir improved them. DIHS itself and the aggravation of hepatitis B by corticosteroid should be kept in mind in cases with dual infection of HBV and HCV treated by antivirals including telaprevir.

Topics: Antiviral Agents; Biomarkers; Coinfection; DNA, Viral; Drug Hypersensitivity Syndrome; Drug Substitution; Drug Therapy, Combination; Glucocorticoids; Guanine; Hepacivirus; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Oligopeptides; Polyethylene Glycols; Prednisolone; Recombinant Proteins; Ribavirin; RNA, Viral; Treatment Outcome; Viral Load; Virus Activation

More than 1% of the Hungarian population is infected with hepatitis B, C, or D viruses. Since 2006 the diagnostics and therapy of these infections are carried out in treatment centers according to national guidelines - since 2010 according to financial protocols. The consensus-based guidelines for 2012 are published in this paper. The guidelines stress the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection is pegylated interferon for 48 weeks or continuous entecavir therapy. The later must be continued for at least 6 months after hepatitis B surface antigen (HBsAg) seroconversion. Tenofovir disoproxil fumarat is not yet reimbursed by the National Health Insurance Fund. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Treatment naive chronic hepatitis C patients should initially receive pegylated interferon and ribavirin dual combination therapy. In genotype 1 infection if response is insufficient at 4 or 12 weeks one of the two new direct acting antivirals (boceprevir or telaprevir) should be added. The length of treatment is usually 48 weeks; in cases of extended early viral response shorter courses are recommended. Previous treatment failure patients with genotype 1 infection should receive a protease inhibitor backed triple combination therapy, mostly for 48 weeks. However, relapsers without cirrhosis and with extended rapid viral response, shorter telaprevir based combination therapy is sufficient. Drug-drug interactions as well as emergence of viral resistance are of particular importance. For genotype 2 or 3 HCV infections 24 weeks, for genotype 4 infections 24, 48 or 72 weeks of pegylated interferon plus ribavirin therapy is recommended in general. The guidelines published here become protocols when published as official publications of the Hungarian Health Authority.

Topics: Adenine; Antiviral Agents; Comorbidity; Consensus; Drug Administration Schedule; Drug Therapy, Combination; Genotype; Guanine; Hepacivirus; Hepatitis B; Hepatitis C; Hepatitis D; Humans; Hungary; Interferon-alpha; Interferons; Lamivudine; Oligopeptides; Organophosphonates; Polyethylene Glycols; Proline; Recombinant Proteins; Ribavirin; RNA, Viral; Tenofovir; Time Factors; Treatment Outcome

The course and outcome of acute viral hepatitis in liver transplanted patients with hepatitis C recurrence are unknown. Here we describe a patient who presented with acute hepatitis B infection while on treatment with peg-interferon and ribavirin for hepatitis C recurrence after liver transplantation. A nucleoside analogue was added (entecavir) and the patient cleared hepatitis C virus (HCV) infection and seroconverted to anti-HBs. In this case, the acute hepatitis B virus (HBV) infection might have contributed to the clearance of HCV, the concomitant immunosuppression might have lead to the slow clearance of HBV infection, and the combined antiviral therapy has helped in the resolution of both infections. Hepatitis B vaccination should be recommended in susceptible patients waiting for liver transplantation.

Topics: Aged; Antibodies, Viral; Antiviral Agents; Drug Therapy, Combination; Guanine; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Male; Polyethylene Glycols; Recombinant Proteins; Recurrence; Ribavirin; Superinfection; Treatment Outcome; Viral Load

Chronic hepatitis B (CHB) is a dynamic disease that is influenced by host and virological factors. The management of CHB has become more complex with the increasing use of long-term oral nucleos⁄tide analogue antiviral therapies and the availability of novel diagnostic assays. Furthermore, there is often a lack of robust data to guide optimal management such as the selection of therapy, duration of treatment, potential antiviral side effects and the treatment of special populations. In November 2011, the Canadian Liver Foundation and the Canadian Association for the Study of the Liver convened a consensus conference to review the literature and analyze published data, including other international expert guidelines on CHB management. The proceedings of the consensus conference are summarized and provide updated clinical practice guidelines to assist Canadian health care providers in the prevention, diagnosis, assessment and treatment of CHB.

Topics: Adenine; Allied Health Personnel; Antibodies, Viral; Antiviral Agents; Canada; Coinfection; Drug Resistance, Viral; Drug Therapy, Combination; Female; Guanine; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis C; Humans; Interferons; Kidney Diseases; Liver; Organophosphonates; Pregnancy; Pregnancy Complications, Infectious; Tenofovir