entecavir and Viremia

Topics: Antiviral Agents; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms; Treatment Outcome; Viremia

Topics: Alanine Transaminase; Antiviral Agents; Aspartate Aminotransferases; DNA, Viral; Double-Blind Method; Drug Resistance, Viral; Guanine; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; HIV Infections; Humans; Lamivudine; Liver Cirrhosis; Liver Transplantation; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome; Viremia

Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood.. This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.. The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%-2.88%) and an annual rate of 0.22% (.17%-.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA <2000 IU/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80-5.49]), elevated serum alanine aminotransferase >200 U/L (3.68 [2.07-6.53]), serum bilirubin (1.11 per mg/dL; [1.06-1.17 mg/dL]), and fatty liver (1.84 [1.03-3.29]).. HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.

Topics: Alanine Transaminase; Antiviral Agents; Bilirubin; China; Cohort Studies; DNA, Viral; Fatty Liver; Female; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Incidence; Male; Middle Aged; Tenofovir; Treatment Outcome; Viremia

Suppression of hepatitis B virus (HBV) DNA is more potent, and occurrence of resistant strain is rare with entecavir than lamivudine, but whether these merits result in a more favourable outcome in HBV-related decompensated cirrhosis patients is unclear.. To compare virologic response, changes in liver function, clinical course and predictive factors for early mortality after treatment between patients treated with lamivudine and those with entecavir in HBV-related decompensated cirrhosis patients.. HBV-related decompensated cirrhosis patients [Child-Turcotte-Pugh (CTP) score ≥ 7] treated with either lamivudine or entecavir were enrolled. Serum HBV DNA levels, CTP score and Model for End-stage Liver Disease (MELD) score were monitored every 3 months.. Eighty-six patients were enrolled; mean age was 54 ± 11 years, and 63 (73.3%) patients were men; 41 (47.7%) and 45 (52.3%) patients were assigned to the lamivudine group and entecavir group respectively. Although suppression of serum HBV DNA level was more potent in the entecavir group, CTP or MELD scores during the course of treatment did not differ between the two groups. Similarly, 6-month survival rates did not differ between the two groups (95.1 vs 93.2%, P = 0.684). Baseline CTP score and MELD score at 3 months of treatment were significantly associated with 6-month mortality. The 6- and 12-month mortality rates for patients with baseline CTP score ≥ 11 and MELD score ≥ 17.5 after 3 months of treatment were 42.9 and 61.9% respectively.. Although HBV DNA suppression was more potent in the entecavir group than the lamivudine group, early mortality rates did not differ between the two groups. The baseline CTP score and MELD score 3 months after initiating antiviral treatment were significant predictors of early mortality.

Topics: Adult; Aged; Antiviral Agents; Guanine; Hepatitis B; Hepatitis B virus; Humans; Lamivudine; Liver Cirrhosis; Middle Aged; Multivariate Analysis; Republic of Korea; Viremia

Topics: Adult; Anti-HIV Agents; Drug Resistance, Viral; Guanine; Hepatitis B, Chronic; HIV; HIV Infections; Humans; Male; Middle Aged; Pilot Projects; Treatment Outcome; Viremia

About 20% of patients receiving nucleos(t)ide analogues treatment experienced low-level viraemia (LLV), which is associated with progression of liver fibrosis and high risk of hepatocellular carcinoma. We aimed to evaluate the effectiveness and safety of switching from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in ETV-treated patients with LLV.. In this prospective study, ETV-treated patients with LLV, presented to our hospital from December 2018 to October 2019, were enrolled. Switching to TAF or continuing ETV was given. The primary effectiveness endpoint was complete virological response (CVR) at 24 weeks, and the safety endpoint was the first occurrence of any clinical adverse event during the treatment.. Totally, 211 patients were recruited and propensity score matching (PSM) generated 75 patients in either TAF or ETV group. After PSM, baseline characteristics were balanced in two groups. After 24-week treatment, the CVR and ALT normalization in TAF group were 62.7% and 47.6%, which were higher than 9.3% and 10.5% in ETV group (OR 16.4, 95% CI 6.6-40.0, P < .001) respectively. Subgroup analysis showed that switching to TAF achieved favours CVR regardless of the status of sex, age, CHB family history, HBV DNA, HBeAg and cirrhosis, whereas alcohol consumption and diabetes mellitus might compromise the CVR of switching to TAF. Both therapies were well tolerated and had satisfying renal safety.. For ETV-treated patients with LLV, switching to TAF is safe enough and superior compared with continuing ETV monotherapy regarding both virological and biochemical benefits.

Topics: Adenine; Alanine; Antiviral Agents; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Prospective Studies; Tenofovir; Treatment Outcome; Viremia

As current interventions for chronic hepatitis B (CHB) rarely induce cure, more effective drugs are needed. Short-term treatment of woodchucks with the novel immunomodulator AIC649, a parapoxvirus-based stimulator of toll-like receptor 9 dependent and independent pathways, has been shown to reduce viral DNA and surface antigen via a unique, biphasic response pattern. The present study evaluated long-term AIC649 treatment in combination with Entecavir for potency and safety in woodchucks. AIC649 monotreatment induced modest reductions in serum viral DNA and surface and e antigens that were associated with the same biphasic response pattern previously observed. Entecavir monotreatment reduced transiently viremia but not antigenemia, while AIC649/Entecavir combination treatment mediated superior viral control. Undetectability of viral antigens and elicitation of antibodies in AIC649/Entecavir-treated woodchucks correlated with the expression of interferons and suppression of viral replication in liver. Combination treatment was well tolerated, and liver enzyme elevations were minor and transient. It was concluded that the AIC649-mediated effects were most likely based on an improvement and/or reconstitution of antiviral immune responses that are typically deficient in CHB. As a combination partner to Entecavir, the antiviral efficacy of AIC649 was markedly enhanced. This preclinical study supports future evaluation of AIC649 for treatment of human CHB.

Topics: Animals; Antiviral Agents; Disease Models, Animal; DNA, Viral; Drugs, Investigational; Guanine; Hepatitis B Virus, Woodchuck; Hepatitis B, Chronic; Immunologic Factors; Marmota; Treatment Outcome; Viremia; Virus Replication

Topics: Guanine; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Prognosis; Viremia

Topics: Antiviral Agents; Carcinoma, Hepatocellular; Guanine; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms; Viremia

Topics: Anilides; Antiviral Agents; Carbamates; Coinfection; Cyclopropanes; Drug Therapy, Combination; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Protease Inhibitors; Ribavirin; Ritonavir; Sulfonamides; Valine; Viral Load; Viral Nonstructural Proteins; Viremia; Virus Activation

The long-term clinical impact of low-level viremia (LLV; <2,000 IU/mL) is not well understood. As a result, it is unclear whether the development of LLV during entecavir monotherapy requires a change in therapy. A retrospective cohort of 875 treatment-naive chronic hepatitis B virus (HBV) monoinfected patients (mean age 47.7 years, male = 564 [65.5%], cirrhosis = 443 [50.6%]) who received entecavir monotherapy were analyzed for the development of hepatocellular carcinoma (HCC). The HCC risk was compared between patients who maintained virological response (MVR), defined by persistently undetectable HBV DNA (<12 IU/mL), and patients who experienced LLV, defined by either persistent or intermittent episodes of <2,000 IU/mL detectable HBV DNA. During a median 4.5 years of follow-up (range 1.0-8.7 years), HCC was diagnosed in 85 patients (9.7%). HCC developed more frequently in patients who experienced LLV than MVR (14.3% versus 7.5% at 5 years, P = 0.015). The hazard ratio comparing those with LLV to MVR was 1.98 (95% confidence interval = 1.28-3.06, P = 0.002, adjusted for age, sex, hepatitis B e antigen, baseline HBV DNA levels, and cirrhosis). Among patients with cirrhosis, those with LLV exhibited a significantly higher HCC risk than those with MVR (HCC incidence rate at 5 years 23.4% versus 10.3%, adjusted hazard ratio = 2.20, 95% confidence interval 1.34-3.60; P = 0.002). However, for patients without cirrhosis, there was no significant difference in the HCC risk between LLV and MVR.. LLV observed during entecavir monotherapy was associated with a higher risk of HCC, especially for those with cirrhosis, indicating that LLV during potent antiviral therapy is consequential. (Hepatology 2017;66:335-343).

Topics: Adult; Age Factors; Analysis of Variance; Antiviral Agents; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cohort Studies; DNA, Viral; Female; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Republic of Korea; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Factors; Viral Load; Viremia

Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients.. In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB.. Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0-4). Glomerular filtration rate (GFR) was <50 mL/min in 7 patients (54%). Two patients were started on de novo ETV before transplant. Eleven previously treated patients were switched to TDF (n = 9) or LdT (n = 2). Median treatment duration was 33 months (range 1-71). HBV DNA remained suppressed in 6 patients and became undetectable in 5. Aminotransferases went down to the normal range in all patients, with a single flare in 1 patient. One patient lost hepatitis B surface antigen. No cases occurred of hepatic decompensation, hepatocellular carcinoma, or liver-related death. The GFR remained largely stable, and no cases of TDF-related hyper-phosphaturia were observed.. This study indicates that newer antivirals are effective and safe in HTR with CHB.

Topics: Adult; Aged; Antiviral Agents; Cohort Studies; DNA, Viral; Female; Follow-Up Studies; Guanine; Heart Transplantation; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Prospective Studies; Telbivudine; Tenofovir; Thymidine; Treatment Outcome; Viremia

The current strategies for hepatitis B virus (HBV) post-exposure prophylaxis (PEP) are not generally available in remote and rural areas of developing countries and/or carry potential risks for infection with blood-borne transmitted pathogens. Nucleotide analogues (NAs) are successfully used for human immunodeficiency virus PEP, and maybe effective for HBV PEP. In this study, we tested the NA-based strategies for HBV PEP using the Chinese woodchuck model.. Chinese woodchucks were inoculated intravenously with different doses of woodchuck hepatitis virus (WHV). A deoxyguanosine analogue entacavir (ETV), a DNA vaccine pWHcIm, or ETV plus pWHcIm were applied to the infected animals 24h later. Twenty weeks later, the animals were re-challenged with WHV to test for the presence of immunity against WHV.. Inoculation with different WHV doses had a strong influence on the course of WHV infection; NA alone or in combination with a DNA vaccine completely prevented viremia after a high dose of WHV inoculation in Chinese woodchucks and induced partial or complete protective immunity, respectively.. NA-based PEP strategies (NA alone or in combination with vaccine) may be an alternative of HBV PEP, especially in those living in the remote and rural areas of the developing countries and the non-responders to the current vaccine, and may be valuable in the PEP of HBV and HIV co-infection after occupational and non-occupational exposure. Further clinical studies are warranted to confirm the valuable of NA-based strategies in HBV PEP.

Topics: Animals; Antiviral Agents; Disease Models, Animal; Drug Therapy, Combination; Guanine; Hepadnaviridae Infections; Hepatitis B Virus, Woodchuck; Post-Exposure Prophylaxis; Treatment Outcome; Vaccination; Viral Vaccines; Viremia

The main purpose of therapy for infectious diseases is restoration or protection of the patient's health, but suppression or elimination of infectious agents is also important. In two well-defined situations, reduction of potential infectivity may be the main reason for therapy in hepatitis B virus (HBV) carriers who do not suffer from significant disease: (1) healthcare providers who perform exposure-prone procedures to prevent transmission of HBV to individuals, and (2) pregnant women in the third trimester to prevent transmission to the fetus. This article describes the necessity to recognize highly viremic HBV-infected individuals in these situations, the methods to estimate the risk of transmission, and the therapeutic possibilities to prevent transmission. With today's methods of monitoring HBV DNA, it is possible to reliably estimate the risk of transmission. The drugs entecavir or tenofovir are able to suppress infectivity of HBV carriers to levels acceptable for healthcare providers performing exposure-prone procedures. According to the CDC, 'chronic HBV infection in itself should not preclude the practice or study of medicine, surgery, dentistry, or allied health professions.' Treatment of pregnant women with very high levels of HBV DNA prevents the transmission to the fetus and further if the newborn receives immediate active/passive immunization against HBV.

Topics: Adenine; Antiviral Agents; DNA, Viral; Female; Guanine; Health Personnel; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Infectious Disease Transmission, Professional-to-Patient; Infectious Disease Transmission, Vertical; Lamivudine; Organophosphonates; Pregnancy; Pregnancy Complications, Infectious; Reverse Transcriptase Inhibitors; Telbivudine; Tenofovir; Thymidine; Viral Load; Viremia

Long-term viral suppression is a major goal to prevent disease progression in patients with HBV. Aim of this study was to investigate the efficacy and safety of entecavir plus tenofovir combination in 57 CHB partial responders or multidrug resistant patients.. Investigator-initiated open-label cohort study. Quantitative HBV-DNA measurement and resistance testing (line-probe-assays and direct-sequencing) at baseline and every 3 months.. Fifty seven patients (37 HBeAg+), median age 45 years, previously treated with a median of three lines of antiviral therapy (range 1-6), 24/57 with advanced liver disease, were included. Median ALT at baseline was 1.0 ULN (range 0.3-22) and HBV-DNA 1.5 × 10(4)IU/ml (range 500-1 × 10(11)IU/ml). Median treatment duration of combination therapy was 21 months. HBV-DNA level dropped 3 logs (median, range 0-8 log; p<0.0001), 51/57 patients became HBV-DNA undetectable, median after 6 months (95% CI, 4.6-7). The probability for HBV DNA suppression was not reduced in patients with adefovir or entecavir resistance or in patients with advanced liver disease. Viral suppression led to decline in ALT (median 0.7 ULN; range 0.2-2.4; p=0.001). Five patients lost HBeAg (after 15, 18, 20, 21, and 27 months, respectively), one patient showed HBs-seroconversion. Patients with advanced disease did not show clinical decompensation, two patients with cirrhosis and undetectable HBV DNA developed HCCs. No death, newly induced renal impairment or lactic acidosis were reported.. Rescue therapy with entecavir and tenofovir in CHB patients harboring viral resistance patterns or showing only partial antiviral responses to preceding therapies was efficient, safe, and well tolerated in patients with and without advanced liver disease (249).

Topics: Adenine; Adult; Aged; Antiviral Agents; Cohort Studies; Drug Resistance, Viral; Drug Therapy, Combination; Female; Follow-Up Studies; Guanine; Hepatitis B, Chronic; Humans; Internationality; Male; Middle Aged; Organophosphonates; Retrospective Studies; Tenofovir; Treatment Outcome; Viremia; Young Adult

We report a case of an immunocompromised patient affected by chronic hepatitis B virus (HBV) with high basal HBV viremia (>8 log(10) IU/ml) who failed an entecavir regimen, despite the absence of primary or secondary drug resistance mutations. The patient achieved sustained virological success (serum HBV DNA <12 IU/ml) when tenofovir was added to the treatment. This case highlights the difficulty in choosing an optimal therapy in such specific conditions and supports the concept of tailoring therapy (including combination regimens) on the basis of the particular conditions of each individual patient.

Topics: Adenine; Adult; Alanine Transaminase; Antiviral Agents; Bone Marrow; DNA, Viral; Drug Therapy, Combination; Female; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Immunocompromised Host; Italy; Organophosphonates; Tenofovir; Treatment Outcome; Viremia

Recently, we reported on three patients with chronic hepatitis B virus (HBV) infection for whom adefovir (ADF) therapy virologically failed, most likely due to a preexisting rtI233V HBV polymerase mutation. Here, we describe two further patients with chronic HBV infection who were found to develop the rtI233V mutation after initiation of ADF therapy. These patients represent the first cases known so far in which the rtI233V ADF resistance mutation evolved under persistent HBV replication during HBV therapy with ADF. Interestingly, one of the previously described patients, who was initially successfully switched from ADF to tenofovir (TDF) and became virologically suppressed subsequently, experienced a moderate but remarkable rebound of HBV viremia after switching from TDF to entecavir, due to the emergence of renal toxicity. Thus, we provide evidence for the selection and counterselection of the rtI233V ADF resistance mutation during antiviral therapy.

Topics: Adenine; Adult; Amino Acid Sequence; Amino Acid Substitution; Antiviral Agents; Drug Resistance, Viral; Female; Guanine; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Molecular Sequence Data; Mutation, Missense; Organophosphonates; Selection, Genetic; Sequence Alignment; Tenofovir; Treatment Failure; Viremia; Young Adult

To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.. Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1-12, 13-24 and 24-48, respectively. Multilevel modelling was used to analyse the relationship between these variables.. Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 10(7) copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8+ T cells and increase in CD4+ T cells were found from week 12. Both parameters and CD4+/CD8+ ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4-48 week). After 4 weeks of therapy, for each log10 scale decrement of HBV DNA, the percentage of CD4+ lymphocyte was increased by 0.49 and that of CD8+ decreased by 0.51.. T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.

Topics: Adolescent; Adult; Antiviral Agents; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cohort Studies; DNA, Viral; Female; Guanine; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Function Tests; Male; Middle Aged; Models, Biological; Multivariate Analysis; Regression Analysis; T-Lymphocyte Subsets; Viral Load; Viremia; Virus Replication