Review of Current and Potential Treatments for Chronic Hepatitis B Virus Infection.
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ABSTRACT:
SUBMITTER: Tsai E
PROVIDER: S-EPMC8475260 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus (HBV) is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.
| S-EPMC5010840 | biostudies-literature
Project description:ObjectivesTo evaluate the comparative effectiveness of antiviral drugs in adults with chronic hepatitis B monoinfection for evidence-based decision-making.MethodsA systematic review of randomized controlled clinical trials (RCTs) published in English. Results after interferon and nucleos(t)ides analog therapies were synthesized with random-effects meta-analyses and number needed to treat (NNT).ResultsDespite sustained improvements in selected biomarkers, no one drug regimen improved all intermediate outcomes. In 16 underpowered RCTs, drug treatments did not reduce mortality, liver cancer, or cirrhosis. Sustained HBV DNA clearance was achieved in one patient when two were treated with adefovir (NNT from 1 RCT=2 95%CI 1;2) or interferon alpha-2b (NNT from 2 RCTs=2 95%CI 2;4), 13 with lamivudine (NNT from 1 RCT=13 95%CI 7;1000), and 11 with peginterferon alpha-2a vs. lamivudine (NNT from 1 RCT=11 95%CI 7;25). Sustained HBeAg seroconversion was achieved in one patient when eight were treated with interferon alpha-2b (NNT from 2 RCTs=8 95%CI 5;33) or 10--with peginterferon alpha-2b vs. interferon alpha-2b (NNT from 1 RCT=10 95%CI 5;1000). Greater benefits and safety after entecavir vs. lamivudine or pegylated interferon alpha-2b vs. interferon alpha-2b require future investigation of clinical outcomes. Adverse events were common and more frequent after interferon. Treatment utilization for adverse effects is unknown.ConclusionsIndividual clinical decisions should rely on comparative effectiveness and absolute rates of intermediate outcomes and adverse events. Future research should clarify the relationship of intermediate and clinical outcomes and cost-effectiveness of drugs for evidence-based policy and clinical decisions.
| S-EPMC3043173 | biostudies-literature
Project description:During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined.
| S-EPMC4735500 | biostudies-other
Project description:BackgroundSome patients with chronic hepatitis C virus (HCV) infection forego treatment due to concerns about treatment efficacy, treatment duration, and side effects.ObjectiveThe purpose of this study was to quantify patient preferences among possible outcomes associated with new, direct-acting antiviral agents (DAAs) for the treatment of HCV infection and determine which treatment features are most important to patients in making treatment decisions.MethodsAdult participants with a self-reported physician diagnosis of HCV infection in five countries completed a web-enabled, choice-format conjoint analysis survey. The survey presented participants with 20 treatment-choice questions. Each treatment-choice question included a pair of hypothetical treatment profiles with varying levels of six attributes: treatment duration; chance of getting rid of the virus completely (i.e. likelihood of a sustained virologic response [SVR]); weeks on an additional, third medicine (i.e. a DAA); risk of a severe rash; risk of severe anemia; and number of times a day the third medicine is taken. Treatment-choice questions were based on a pre-determined experimental design with known statistical properties. Random-parameters logit was used to estimate preference weights for all attribute levels and the mean relative importance of each attribute.Results284 participants completed the survey. Likelihood of an SVR was the most important outcome to participants, followed by severe anemia risk, severe rash risk, therapy type (a combination of total weeks of treatment and weeks on the third medicine), and dosing of the third medicine. Controlling for other factors, preferences were similar across all therapy types examined.ConclusionPatients with HCV infection indicate a willingness to accept an increased risk of side effects for sufficient improvement in the likelihood of treatment response.
| S-EPMC3714139 | biostudies-literature
Project description:Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty-four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta-analysis of 395 patients showed a pooled SVR rate of 78% (95-CI 72%-84%) after ribavirin treatment. Twenty-five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon-alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon-alpha increases the risk of transplant rejection and should therefore be administered with great caution.
| S-EPMC7898834 | biostudies-literature
Project description:Hepatitis C virus (HCV) infects 180 million people worldwide and over 4 million people in the United States. HCV infection is a major cause of chronic liver disease and is recognized as a risk factor for clinical cardiovascular disease (CVD). Many studies have shown increased prevalence of cardiac and inflammatory biomarkers in patients with chronic HCV infection (CHC), and though these markers may be used to risk stratify people for cardiac disease in the general population their role in the HCV population is unknown. Patients with CHC have elevated cardiac and inflammatory biomarkers compared to noninfected controls which may play a role in CVD risk stratification. We undertook a systematic review of inflammatory and cardiac biomarkers in people with HCV infection with a focus on the effect of CHC on serum levels of these markers and their utility as predictors of CVD in this population. Medline, EMBASE, and Cochrane databases were searched for relevant articles until June 2019. A total of 2430 results were reviewed with 115 studies included. Our review revealed that HCV infection significantly alters serum levels of markers of inflammation, endothelial function, and cardiac dysfunction prior to HCV treatment, and some of which may change in response to HCV therapy. Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV-infected patients contributing to increased CVD risk.
| S-EPMC7068107 | biostudies-literature
Project description:Viral hepatitis C is responsible for a large burden of disease worldwide. Treatment of hepatitis C infection is currently undergoing a revolution with the development of new direct acting antivirals that offer higher cure rates and fewer side effects than other medications currently available. Treatment options for children, although well-defined and evidence-based, are limited relative to adults as there are few trials regarding the use of these newly developed agents in children. With so much optimism in the development of novel therapeutic options for hepatitis C, it is timely to review and summarize the current standard of care treatment and indications for treatment of chronic hepatitis C in children. We provide here an overview of recent drug developments and their potential for use in children.
| S-EPMC4542086 | biostudies-other
Project description:The human hepatitis B virus (HBV) is a small-enveloped DNA virus causing acute and chronic hepatitis. Despite the existence of an effective prophylactic vaccine and the strong capacity of approved antiviral drugs to suppress viral replication, chronic HBV infection (CHB) continues to be a major health burden worldwide. Both the inability of the immune system to resolve CHB and the unique replication strategy employed by HBV, which forms a stable viral covalently closed circular DNA (cccDNA) minichromosome in the hepatocyte nucleus, enable infection persistence. Knowledge of the complex network of interactions that HBV engages with its host is still limited but accumulating evidence indicates that epigenetic modifications occurring both on the cccDNA and on the host genome in the course of infection are essential to modulate viral activity and likely contribute to pathogenesis and cancer development. Thus, a deeper understanding of epigenetic regulatory processes may open new venues to control and eventually cure CHB. This review summarizes major findings in HBV epigenetic research, focusing on the epigenetic mechanisms regulating cccDNA activity and the modifications determined in infected host cells and tumor liver tissues.
| S-EPMC7174266 | biostudies-literature
Project description:To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection.This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome.The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development.The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.
| S-EPMC5107707 | biostudies-literature
Project description:BACKGROUND:Previous reports show conflicting results regarding hepatitis B virus (HBV) vaccine efficacy in Hepatitis C virus (HCV)-infected individuals. AIMS:To evaluate HBV-vaccine response and identify possible factors that may contribute to lower vaccine efficacy in patients infected with HCV. METHODS:We retrospectively evaluated all patients with chronic HCV infection at Hennepin County Medical Center, in Minneapolis, Minnesota, between 2002 and 2018. We addressed laboratory, liver-related, virus-related as well as vaccine-related variables, and their association to HBV vaccine response. Differences were tested using either a Chi-squared test or a T test to compare means between the two populations. Multivariate regression was modeled as a logistic regression. RESULTS:1506 patients were evaluated, of which 525 received appropriate HBV vaccination and were assessed for response. Among those, 79% were vaccine responders and 21% were non-responders. On multivariate analysis, cirrhosis was associated with lower response to the vaccine (OR 0.6, CI 0.44-0.94). We found no significant differences for vaccine response in relation to smoking (87% vs 86%), IV drug abuse (74% vs 72%), Diabetes Mellitus (26% vs 22%) being on hemodialysis (2% vs.5%), or virus related variables. CONCLUSION:HCV infection seems to impair HBV vaccine response, with cirrhosis being the only identifiable risk factor for hypo-responsiveness among studied clinical and virus-related variables.
| S-EPMC7449383 | biostudies-literature