A randomized double-blind placebo-controlled field trial of ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana (original) (raw)
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Liver safety assessment in clinical trials of new agents for chronic hepatitis B
Journal of Viral Hepatitis, 2019
Investigational agents that reduce or eliminate covalently closed circular DNA (cc-cDNA) or enhance host immunity against hepatitis B virus (HBV)-infected hepatocytes are intended to induce a durable off-treatment clearance of hepatitis B surface antigen (HBsAg) (referred to as functional cure). The aim of this paper was to highlight challenges in interpreting liver safety data in clinical trials of these agents when given alone or in combination regimens. The incidence, grading and management of spontaneous serum ALT flares in untreated chronic HBV patients are reviewed along with a summary of serum ALT flares observed during the registration trials for peginterferon and nucleos(t)ide reverse transcriptase inhibitors. Recommendations regarding the detection, management and interpretation of liver safety biomarker data in future clinical trials as well as suggested inclusion and exclusion criteria for phase 1/2 vs phase 3 studies are provided. Criteria to help classify liver safety signals as being due | 97 FONTANA eT Al.
A Review on Therapeutic Management of Chronic Hepatitis B Infection
The current therapeutic goal in the management of chronic hepatitis B (CHB) infection is to persistently suppress hepatitis B virus (HBV) replication and prevent its progression to liver failure and the development of hepatocellular carcinoma (HCC). At present, the therapeutic strategies for CHB includes either a short course of pegylated-interferon-alfa (PEG-IFNa) and/or a long term course of nucleos(t)ide analogues (NA’s). NA’s are more preferable to PEG-IFNa, majorly for its easier route of administration and excellent tolerance and safety profiles. Entecavir (ETV) and tenofovir (TDF) are the current first line options for its potency to maintain sustained virological response (SVR) in almost 100% of the adherent individuals along with minimal to no long-term resistance. These sustained inhibitions of HBV replication have been shown to be associated with histological improvement, modifying the long-term outcomes. However, HBsAg seroconversion, the best surrogate marker for viral clearance is still unachievable with the current first line agents and hence the risk for hepatocellular carcinoma (HCC) still exists among them. This makes us to still consider, a finite duration of PEG-IFNa that has shown considerable results with regards to HBsAg loss, as an attractive add-on or monotherapy option despite its adverse events profile. Existing evidences do not recommends its usage. However, numerous studies are ongoing and also further studies to evaluate the reliable baseline predictors of response to PEG-IFNa and early on-treatment stopping rules based on age, alanine aminotransferase levels (ALT), HBV DNA levels and HBsAg kinetics would be ideal.
2018
The aims of this study were to compare the efficacy between tenofovir (TDF) and entecavir (ETV) monotherapy for 24 months and to assess the gender differences in the clinical prognosis in Korean patients with chronic hepatitis B (CHB). This study was retrospectively conducted with hepatitis B virus (HBV)-infected patients taking TDF or ETV between July 2012 and June 2016 in Chosun University Hospital, Gwangju, South Korea. Data were collected through the review of Electronic Medical Records. Among 1,450 patients during the study period, 130 were selected based on inclusion and exclusion criteria. At baseline, the rate of hepatitis B envelope antigen (HBeAg)-positivity in TDF was higher than that of HBeAg-positivity in ETV, showing a significant difference (84.4% vs. 57.8%, p = 0.0020). However, these rates in both TDF and ETV became similar at 3 months, and this tendency had continued after 3 months. There were no significant differences in the changes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels during the followup period between TDF and ETV. However, these levels were almost normalized within 3 months, and the normal levels had also been kept after 3 months. Men tended to have more liver cirrhosis or hepatocellular carcinoma than women. ALT levels had been continuously higher in men than in women, showing significant differences at 3, 6, 12, and 24 months. TDF is more likely than ETV to be a potent option for CHB patients with severe liver diseases, especially men, because TDF tended to decrease the parameters related with HBV infection (e.g., ALT, AST, and HBV DNA level) more rapidly within 3 months than ETV.
Evaluation of current treatment recommendations for chronic hepatitis B: A 2011 update
Journal of Gastroenterology and Hepatology, 2011
Background and Aim: Guidelines for the treatment of chronic hepatitis B have been recently updated in the 2009 European Association for the Study of the Liver consensus statement, the 2008 US Panel, the 2008 Asian-Pacific consensus statement, and the 2009 American Association for the Study of Liver Disease practice guidelines. We sought to determine whether these guidelines identified patients who developed hepatocellular carcinoma (HCC) or who died of non-HCC liver-related deaths for antiviral therapy. Methods: The criteria described in the new treatment guidelines were matched to the database of 369 hepatitis B surface antigen-positive patients, in whom 30 developed HCC and 37 died of non-HCC liver-related deaths during a mean follow up of 84 months. Results: Using criteria for antiviral therapy as stated by the four current guidelines, 19-30% of patients who died of non-HCC liver-related complications, and 23-53% of patients who developed HCC, would have been excluded for antiviral therapy. If baseline serum albumin levels of Յ 3.5 g/dL or platelet counts of Յ 130 000 mm 3 were included into the treatment criteria, then 85-94% of patients who developed liver-related complications would have been recommended for antiviral therapy. Also, the addition of precore A1896 mutants and basal core promoter T1762/A1764 mutants would have identified 98.5-100% of these patients. Conclusion: The updated treatment guidelines for hepatitis B still excluded patients who developed serious liver-related complications. The inclusion of baseline serum albumin and platelet counts to current criteria would have identified a majority of these patients for antiviral therapy. These tests should be included into hepatitis B treatment strategies.
Management of chronic hepatitis B
Evidence report/technology assessment, 2008
Synthesize evidence of the natural history of chronic hepatitis B (CHB) and effects and harms of antiviral drugs on clinical, virological, histological, and biochemical outcomes. MEDLINE, electronic databases, and manual searches of systematic reviews. We included original observational studies to assess natural history and randomized controlled trials (RCTs) of adults with CHB published in English to assess treatment effects and harms if they reported mortality, incidence of hepato-cellular carcinoma (HCC), cirrhosis or failure, HBeAg or HBsAg, viral load (HBV DNA), alanine aminotransferase (ALT) levels, histological necroinflammatory and fibrosis scores, and adverse events after interferon alfa-2b, pegylated interferon alfa 2-a, lamivudine, adefovir, entecavir, tenovir or telbivudine. We excluded pregnant women, transplant patients, and individuals undergoing cancer chemotherapy. We calculated relative risk or absolute risk differences at end of treatment and post-treatment. Obser...
Hepatology International - HEPATOL INT, 2008
The natural course of hepatitis B virus (HBV) infection is variable, and chronic hepatitis B (CHB) disease exhibits itself through a spectrum of clinical manifestations. These factors contribute to the challenges faced when managing patients who live with HBV infection. Furthermore, conventional treatment options (e.g., interferon alfa-2a, lamivudine, and adefovir) are moderately effective and can be associated with problems, such as poor tolerability (interferon alfa-2a) and the development of drug resistance (lamivudine). Over the last 5 years, several antiviral agents including entecavir, peginterferon alfa-2a, and telbivudine which are more efficacious and have improved tolerability over previous drugs have become available. The availability of novel antiviral agents and advances in understanding resistance patterns of antiviral agents has resulted in refinement of CHB treatment recommendations and guidelines. More recently, evidence from clinical trials suggests the central importance of virologic suppression as an indicator of treatment outcome and the predictive value of on-treatment HBV DNA levels in response to antiviral therapy. This review highlights the goals of therapy and clinical experience with therapies that are newly licensed or in the late stages of clinical development. Current approaches for treating CHB and new strategies for optimizing response to therapy are also discussed.
Then and now: The progress in hepatitis B treatment over the past 20 years
World Journal of Gastroenterology, 2014
The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this review, we will examine the antiviral drugs and the progresses that have been made with antiviral treatments in the field of CHB.
Antiviral treatment in hepatitis B
Japanese Journal of Gastroenterology and Hepatology, 2021
1. Abstract 1.1. Introduction: Acute hepatitis B remains unrecognized in majority of cases as it usually presents as asymptomatic or mild disease. The usual symptom by which common man recognizes the disease is jaundice but it occurs only in 15-40% of cases of acute hepatitis B, thus leading to under reporting of it. Moreover, in 90-95% of adults, the disease never progresses into chronic phase and they become hepatitis B antigen negative (HbsAg) within six months, thus majority even does not know whether they got infected with acute hepatitis B. Only a subset of acute hepatitis B patients who develop severe disease require antiviral treatment. 1.2. Aims and objectives: The aim of study was to determine the percentage and Clinico-epidemiological profile of acute hepatitis B patients who needed antiviral treatment. 1.3. Materials & Methods: It was an epidemiology based, prospective study conducted at Medical Gastroenterology Department, PGIMS, Rohtak over a period of three years and eleven months. Four hundred and twenty five (425) patients who were found to be having features of acute hepatitis and confirmed to be positive for HbsAg on Enzyme linked Immunoassay test (ELISA) and HBV DNA on PCR testing were enrolled in the study. Out of these 425 patients, the data of fifteen patients requiring antiviral treatment was analyzed. 1.4. Results: There is very less percentage of acute hepatitis B patients who need antiviral treatment but judicious and timely intervention can reduce morbidity and mortality associated with it.
Journal of Clinical Practice and Research, 2024
The objective of this study was to evaluate the long-term efficacy and safety in chronic hepatitis B (CHB) patients who were treated with Tenofovir Alafenamide (TAF) for at least one year. Materials and Methods: A total of 133 patients diagnosed with CHB and treated with TAF between June 2018 and June 2022 were screened. Biochemical, serological, and molecular data, patient complaints, and physical examination findings were scanned. These collected data were reviewed retrospectively to investigate their relationship with TAF. Results: In this study, 78 patients were included. The median (minimum-maximum) age of the patients was 56.5 (24-84) years, and 52.6% of them were male. Of the patients, 74.4% were treatment-experienced and 85.9% were hepatitis B e antigen (HBeAg) negative. Virological response rates at the 12 th , 24 th , and 36 th months were 88.5%, 81.3%, and 100%, respectively. Biochemical response rates at the 12 th , 24 th , and 36 th months were 72.7%, 90.9%, and 90.9%, respectively. Anti-HBe seroconversion with HBeAg loss occurred in two (18.2%) patients. Hepatitis B surface antigen (HBsAg) loss was detected in only one (1.3%) patient. In 39.7% of the patients, a total of 44 symptoms or findings that could be associated with drug adverse events were found. The three most common adverse events were weight gain (11.5%), weight loss (8.9%), and pruritus (8.9%). Treatment was discontinued in one patient (1.3%) due to the detection of hyperlipidemia. Conclusion: TAF is an effective and safe treatment option for CHB, controlling the disease and preventing complications. Further studies are needed, especially to investigate the metabolic effects of TAF.