Guidelines for Prevention and Treatment of Chronic Hepatitis B
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ABSTRACT:
SUBMITTER: Wang G
PROVIDER: S-EPMC8516840 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB.
| S-EPMC4033464 | biostudies-literature
Project description:Hepatitis C virus (HCV) infection is a serious health problem leading to cirrhosis, liver failure and hepatocellular carcinoma. The recent introduction of telaprevir, which was approved in November 2011, in combination with peg-interferon and ribavirin is expected to markedly improve the eradication rate of the virus. However, side effects of triple therapy may be severe. In a phase three III clinical trial, 2250 mg of telaprevir, which is the same dosage used in clinical trials in Western countries, was given to Japanese patients. As this dosage is considered to be relatively high for Japanese patients, who typically have lower weight than patients in Western countries, reduction of telaprevir is recommended in the 2012 revision of the guidelines established by the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis published by the Ministry of Health, Labour and Welfare of Japan. Other protease inhibitors with fewer side effects are now in clinical trials in Japan. Alternatively, treatment of patients with combination of direct acting antivirals without interferon has been reported. In this review we summarize current treatment options in Japan and discuss how we treat patients with chronic HCV infection.
| S-EPMC3698425 | biostudies-literature
Project description:Autoimmune hepatitis affects patients of all ages and gender, across all geographic regions. Although still rare, its incidence and prevalence are increasing. Genetic predisposition conveyed by human leucocyte antigen is a strong risk factor for the disease and may be responsible in part for the wide variation in presentation in different geographic regions. Our understanding of the underlying pathogenic mechanisms is evolving and may lead to development of more targeted immunotherapies. Diagnosis is based on elevated levels of serum aminotransferases, gamma globulins, autoantibodies and characteristic findings on histology. Exclusion of other causes of chronic hepatitis is important. Although undiagnosed disease is associated with poor outcomes, it is readily treatable with timely immunosuppressive therapy in the majority of patients. International guidelines are available to guide management but there exists a disparity in the standard treatment regimens. This minireview aims to review the available guidelines and summarize the key recommendations involved in management of this complex autoimmune disease.
| S-EPMC6323516 | biostudies-other
Project description:Adherence to the American Association for the Study of Liver Disease (AASLD) guidelines for the management of chronic hepatitis B (CHB) has not been systematically assessed. We sought to comprehensively evaluate adherence to five key areas of these guidelines. We also evaluated physician and patient factors underlying nonadherence, and predictors of nonadherence such as physician type, patient demographic factors, and phase of CHB infection.Nine hundred and sixty-two adult patients were retrospectively identified. Each patient chart was reviewed in detail. The primary outcome was adherence to five areas of the AASLD guidelines: (i) timely alanine aminotransferase (ALT)/hepatitis B virus DNA level checks needed to monitor inactive carrier and immune-tolerant phases; (ii) liver biopsy to guide decisions on initiating treatment; (iii) treatment initiation when indicated; (iv) hepatocellular carcinoma (HCC) screening; (v) testing for hepatitis A virus (HAV) immunity, HIV, and hepatitis C virus (HCV) co-infections.Sixty percent did not undergo clinically indicated liver biopsies, largely owing to physician nonadherence. Eighty-nine percent of these missed biopsies were needed to further assess possible e-antigen-negative CHB. A high treatment initiation rate was found for the treatment eligible, but 121 patients had unclear treatment eligibility as they warranted, but did not undergo, liver biopsy. Forty-five percent did not have timely HCC screening, although gastroenterology physicians had the highest odds of adherence, and 29% did not have timely CHB lab assessment; patients seen by gastroenterologists had twice the odds compared with primary care physicians of undergoing timely lab monitoring. Thirty-five, 24, and 54% were not tested for HAV, HCV, and HIV co-infections.Our findings show remarkably poor adherence to AASLD guidelines, particularly in the areas of liver biopsy, timely HCC and ALT monitoring, and testing for co-infection. These findings call for greater efforts to meet physician knowledge gaps, incorporation of decision support tools, and improved communication among providers.
| S-EPMC4624277 | biostudies-literature
Project description:Findings among a cohort of 26 patients who had hematologic malignancies and hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis. However, a 3-month course of ribavirin can induce a rapid viral clearance, reducing the risk for chronic hepatitis and enabling continuation of cytotoxic treatments for underlying malignancies.
| S-EPMC4517705 | biostudies-literature
Project description:BackgroundThe occurrence of hepatocellular carcinoma (HCC) is a major concern during antiviral therapy for chronic hepatitis B. There are conflicting opinions regarding the effects of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on HCC prevention. We assessed these two antiviral medications for preventing HCC in treatment-naïve patients with chronic hepatitis B.MethodsWe conducted a retrospective cohort study using nationwide claims data from the Korea Health Insurance Review and Assessment Service. We included 55,473 treatment-naïve adult cases where ETV or TDF treatment was started between 2013 and 2017 (cohort 1). The ETV and TDF groups were matched 1:2 based on age, sex, comorbidities, hospital type, and index date year. Patients were followed up until December 2018. The outcome was the development of HCC. Subgroup analyses were conducted according to sex, age, hospital type and the presence of cirrhosis. We also compared the outcomes of patients who had started antiviral therapy during the 2012-2014 period (cohort 2).ResultsThe matched participants (18,491 in the ETV and 36,982 in the TDF groups) were a part of the study for, on average, 41.2 months. The incidence of HCC did not differ significantly between the ETV (1.46 per 100 patient-years) and the TDF (1.36 per 100 patient-years) treatments (hazard ratio, 0.93; 95% confidence interval, 0.86-1.01; P = 0.081). By contrast, HCC incidence was significantly higher in the ETV group than tenofovir group of cohort 2.ConclusionIn patients with chronic hepatitis B, the ETV treatment did not result in a higher rate of HCC than the TDF treatment.
| S-EPMC8042481 | biostudies-literature
Project description:Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFN-alpha) and ribavirin. It achieves a sustained viral clearance in only 50–60% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFN-alpha. In patients with a rapid virological response to treatment, pegIFN-alpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFN-alpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway. Keywords: Comparison of human patient biopses before and after interferon treatment
2008-04-17 | GSE11190 | GEO
Project description:Over the last decade, the standard of care for the treatment of chronic hepatitis C has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin (RBV) which results in sustained virological response (SVR) rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Currently, there are rapid and continuous developments of numerous new agents against hepatitis C virus (HCV), which are the focus of this review. Boceprevir and telaprevir, two first-generation NS3/4A HCV protease inhibitors, have been recently licensed in several countries around the world to be used in combination with PEG-IFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, compared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naïve genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-naïve patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events (anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir), new drug interactions and increasing difficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG-IFN/RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. Preliminary data suggest that the treatment of chronic HCV patients with well tolerated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.
| S-EPMC3496882 | biostudies-other
Project description:Hepatitis C is a major health care problem plagued by the lack of a truly effective therapy. To date, the combination of interferon and ribavirin has provided the best chance of viral eradication. However, this therapy is expensive, has multiple side effects and works in less than half of patients. New strategies need to be developed to deal with the increasing burden of hepatitis C-related disease, and we anxiously await the arrival of new drugs such as helicase and protease inhibitors.Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/BF03405103 and is accessible for authorized users.
| S-EPMC6979812 | biostudies-literature
Project description:Chronic hepatitis B infection remains a serious global health threat, contributing to a large number of deaths through liver cirrhosis and hepatocellular carcinoma. Current treatment does not eradicate disease, and therefore new treatments are urgently needed. In acute hepatitis B virus (HBV) a strong immune response is necessary to clear the virus, but in chronic infection the immune response is weakened and dysfunctional. Therapeutic vaccination describes the process of inoculating individuals with a non-infective form of viral antigen with the aim of inducing or boosting existing HBV-specific immune responses, resulting in sustained control of HBV infection. In this review we outline the rationale for therapeutic vaccination in chronic HBV infection, discuss previous and ongoing trials of novel HBV therapeutic vaccine candidates and outline strategies to improve vaccine efficacy going forward.
| S-EPMC8274149 | biostudies-literature