Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

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 individualpatient 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.

Cost of treating chronic hepatitis B:Comparison of current treatment guidelines

AIM:To compare program costs of chronic hepatitis B(CHB) screening and treatment using Australian and other published CHB treatment guidelines.METHODS:Economic modeling demonstrated that in Australia a strategy of hepatocellular cancer(HCC) prevention in patients with CHB is more cost-effective than current standard care,or HCC screening.Based upon this model,we developed the B positive program to optimize CHB management of Australians born in countries of high CHB prevalence.We estimated CHB program costs using the B positive program algorithm and compared them to estimated costs of using the CHB treatment guidelines published by the AsianPacific,American and European Associations for the Study of Liver Disease(APASL,AASLD,EASL) and those suggested by an independent United States hepatology panel.We used a Markov model that factored in the costs of CHB screening and treatment,individualized by viral load and alanine aminotransferase levels,and calculated the relative costs of program components.Costs were discounted by 5% and calculated in Australian dollars(AUD).RESULTS:Using the B positive algorithm,total program costs amount to 13 979 224 AUD,or 9634 AUD per patient.The least costly strategy is based upon using the AASLD guidelines,which would cost 34% less than our B positive algorithm.Using the EASL and the United States Expert Group guidelines would increase program costs by 46%.The largest expenditure relates to the cost of drug treatment(66.9% of total program costs).The contribution of CHB surveillance(20.2%) and HCC screening and surveillance(6.6%) is small-and together they represent only approximately a quarter of the total program costs.CONCLUSION:The significant cost variations in CHB screening and treatment using different guidelines are relevant for clinicians and policy makers involved in designing population-based disease control programs.

Current hepatitis B treatment guidelines and future research directions

Hepatitis B virus （HBV） infection causes a tremendous clinical burden across the world with more than half a million people dying annually from HBV related disease. Significant advances have been made in HBV treatment in the past decade and several guidelines have been published by professional societies and expert panels. Although these recommendations have been valuable to help optimize HBV treatment, there is discordance in treatment criteria and many patients infected with HBV may fall outside of these recommendations. This paper systematically reviews the natural history of the disease and compares and contrasts the recommendations for initiation of treatment from the various societies. There is also discussion of special groups that require particular consideration and some of the open research questions and future research directions within the field.

2016 Chinese expert consensus and guidelines for the diagnosis and treatment of papillary thyroid microcarcinoma

The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,

Adoptability and limitation of cancer treatment guidelines： a Chinese oncologist＇s perspective

In recent years, great progress has been made in the treatment of cancer; one of the significant reasons isthe wide adaptation and implementation of standardized treatment based on high-level clinical evidence. Undoubtedly, the advent of guidelines that represent the achievement of the latest and highest quality clinical studies made a significant contribution to the improvement of cancer treatment and management. Aside from cancer patient care, guidelines have also been widely used as standards diagnosis and treatment or primary references in the of other diseases. Numerous guidelines are being enacted each year by a variety of guideline-makers, including national, regional and international academic organizations, medical associations, as well as research institutions and hospitals.

Perspective on the practical indications of endoscopic submucosal dissection of gastrointestinal neoplasms

Endoscopic submucosal dissection (ESD) is a new endoluminal therapeutic technique involving the use of cutting devices to permit a larger resection of the tissue over the muscularis propria. The major advantages of the technique in comparison with polypectomy and endoscopic mucosal resection are controllable resection size and shape and en bloc resection of a large lesion or a lesion with ulcerative findings. This technique is applied for the endoscopic treatment of epithelial neoplasms in the gastrointestinal tract from the pharynx to the rectum. Furthermore, some carcinoids and submucosal tumors in the gastrointestinal tract are treated by ESD. To determine the indication, two aspects should be considered. The first is a little likelihood of lymph node metastasis and the second is the technical resectability. In this review, practical guidelines of ESD for the gastrointestinal neoplasms are discussed based on the evidence found in the literature.

Guidelines for diagnosis and treatment of HIV/AIDS in China (2005)

Acquired immunodeficiency syndrome （AIDS）, ,caused by the human immunodeficiency virus （HIV）, has become a major public health issue in China. It not only posesses formidable challenges for the health of the Chinese people, but has also influenced China＇s economic development and social stability.

The Japanese Clinical Practice Guidelines for intrahepatic cholangiocarcinoma: a comparison with Western guidelines

The Liver Cancer Study Group of Japan(LCSGJ)recently published the first version of the clinical practice guidelines for intrahepatic cholangiocarcinoma(iCCA)(1).The study group followed the GRADE methodology for evidence-based medicine.Japan is a world leader in the treatment of cholangiocarcinoma,with Japanese medical centers realizing superior results compared to other developed countries and many landmark articles originating from these centers.While there are differences between the Japanese iCCA population and patients in other countries,these guidelines contain important lessons for healthcare providers across the world.

IMPACT OF CHINESE GUIDELINES FOR MANAGEMENT OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION ON OUTCOMES OF HOSPITALIZED PATIENTS

Background The first Chinese guidelines for the diagnosis and management of patients with acute myocardial infarction （AMI） were issued by the Cardiovascular Branch of the Chinese Medical Association, the Editorial Board of the Chinese Journal of Cardiology, and the Editorial Board of the Chinese Circulation Journal in December 2001. However, it is still unclear whether these guidelines have produced a major impact on clinical practice and patient outcomes. The purpose of this study was to evaluate the impact of these guidelines on the management and prognosis of Chinese patients with AMI. Methods A retrospective study was carried out in patients with AMI who were admitted to Qilu Hospital of Shandong University from January 1994 to December 2004. Patients were divided into two groups： group A included patients admitted from January 1994 to December 2001, and group B comprised those admitted from January 2002 to December 2004. Therapeutic approaches and the occurrence rate of angina pectoris, reinfarction, heart failure and death during hospitalization were compared between two groups. Results A total of 1783 patients including 1208 cases in group A and 575 cases in group B were enrolled in this study. No significant difference was found in baseline characteristics between group A and group B patients （all P〉0.05）. There were more patients undergoing reperfusion therapy within the first 24 hours after symptom onset in group B than in group A （35.8% vs 21.7%, P〈0.001） . Administration of β-blockers, angiotensin-converting-enzyme inhibitors （ACEIs）, angiotensin receptor blockers （ARBs）, statins, and heparins were more commonly seen in group B than in group A （P〈 0.001）. There were no significant differences in the use of nitrates or antiplatelet drugs between groups A and B （98.8% vs. 97.9%, P=0.172, and 97.4% vs 98.6%, P=0.113, respectively）. In-hospital angina pectoris, heart failure and death were all lower in group B than in group A （ 32.2% vs 41.2%, P〈0.001; 17.2% vs 26.2%, P〈0.001; and 6.4% vs 9.4%, P=0.038, respectively）. There was no significant difference in the rate of reinfarction between group A and B patients （2.2% vs 1.7%, P=0.492）. Conclusions Chinese guidelines for the management of patients with AMI issued in December 2001 resulted in changes in therapy that led to a significant improvement of in-hospital outcomes but not in the rate of reinfarction in patients with AMI.

Guideline on prevention and treatment of chronic hepatitis B in China (2005)

Chronic hepatitis B is one of the most common epidemic diseases in China and has become a majorhealth issue. To help standardize the prevention, diagnosis, and treatment of chronic hepatitis B, the Guideline on prevention and treatment of chronic hepatitis B （abbr. Guideline） was created by a group of appropriate experts belonging to the Society of Hepatology and the Society of Infectious Disease, the Chinese Medical Association according to the principles of evidence-based medicine using the latest clinical research data. The evidence used to formulate the recommendation has been classified into 3 classes and 5 grades, which are indicated by Roman numerals in brackets.

The recommendations of Chinese Parkinson’s disease and movement disorder society consensus on therapeutic management of Parkinson’s disease

Background:Parkinson’s disease(PD)is a chronic,progressive and debilitating disease,which affects over 2.5 million people in China.PD is characterized clinically by resting tremor,muscular rigidity,bradykinesia and postural instability.As the disease progresses,additional complications can arise such as non-motor and neurobehavioral symptoms.Pharmacological treatment and surgical intervention for PD have been implemented in China.Until 10 years ago,there was lack of standardization for the management of PD in different regions and among different physicians,leading to different treatment levels in different regions and different physicians.Since then,the Chinese Parkinson’s Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China,in 2006,2009 and 2014,respectively.Correspondingly,the overall level of treatment for PD in China improved.Objectives:To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence,and to improve the treatment options available to physicians in the management of PD.Summary:A variety of treatment recommendations in the treatment guidelines have been proposed,including physical activity and disease-modifying medication,which should be initiated at the early-stage of the disease.The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs,to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications.Moreover,different treatment strategies should be considered at different stages of the disease.Importantly,treatment guidelines and personalized treatments should be valued equally.A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China.

Implementing a “free” tuberculosis (TB) care policy under the integrated model in Jiangsu, China: practices and costs in the real world

Background:In the 1990s,China introduced a“free”tuberculosis(TB)care policy under the national TB control program.Recently,as a part of a new TB diagnosis and treatment model,it has been recommended that the integrated model scale up.This paper examines whether or not TB designated hospitals in the selected project sites have provided TB care according to the national and local guidelines,and analyzes the actual practices and expenditures involved in completing TB treatment.It also explores the reasons why“free”TB care in China cannot be effectively implemented under the integrated model.Methods:This study was conducted in three counties of Zhenjiang city,Jiangsu province.Mixed methods were used,which comprised reviewing the national and local TB control guidelines,conducting TB patient surveys,collecting TB inpatient and outpatient hospital records,and conducting qualitative interviews with stakeholders.Descriptive statistics were used for quantitative data analysis across counties and in order to compare patients who received only outpatient care and those who received both outpatient and inpatient care.The chi-square test and analysis of variance were performed where necessary.Qualitative data were analyzed using the framework approach.Results:Although the national TB care guidelines recommend outpatient care as a basis for TB treatment in China,we found high hospital admission rates for TB patients ranging from 39%in Yangzhong county to 83%in Dantu county.Almost all outpatient TB patients paid for lab tests and over 80%paid for liver protection drugs and around 70%paid for image examinations.These three components accounted for three-quarters of the total outpatient expenditure.For patients who received only outpatient care,the total expenditure upon completion of TB treatment was on average 1,135 Chinese yuan.For patients who received outpatient and inpatient care,the total expenditure upon completion of TB treatment was 11,117 Chinese yuan.Conclusion:The“free”TB care policy under the integrated model has not been effectively implemented in China.There has been substantial spending on non-recommended services,examinations,and drugs for TB treatment.