Updates in the treatment of chronic hepatitis B

published_or_final_versio

Tenofovir disoproxil fumarate for the treatment of chronic hepatitis B monoinfection

Introduction: Resistance in nucleoside/nucleotide analog (NA) therapy has always been a challenge in the management of chronic hepatitis B (CHB). Clinical studies: Initially developed for the treatment of HIV infection, early in vitro and clinical observational studies had shown tenofovir disoproxil fumarate (TDF) to be also active against CHB. Recent data from various multicenter phase 3 and 4 clinical trials have confirmed TDF being able to achieve a high viral suppression in both NA-naive and -experienced CHB patients. There are also emerging data on the efficacy of TDF in decompensated CHB. Although there are in vitro studies identifying certain mutation loci associated with a reduced susceptibility to TDF, there have so far been no reports of virologic resistance to TDF in clinical studies. TDF has a favorable safety profile, although more long-term data would be needed. Conclusions: TDF has the makings of an 'ideal' first-line drug for the treatment of CHB. © 2011 Asian Pacific Association for the Study of the Liver.postprin

Future prevention and treatment of chronic hepatitis B infection

Vaccination for hepatitis B virus (HBV) infection and treatment for chronic hepatitis B, while effective for primary prevention and control of the disease, still have their limitations. Global coverage of HBV immunization needs improvement. Several patient populations are noted to have suboptimal seroprotective rates after HBV vaccination. There are currently several potential new vaccines undergoing animal and human studies, most notably vaccines containing immunostimulatory DNA sequences. Long-term nucleoside analogue therapy is necessary in achieving permanent virologic suppression. Potential new treatments explore new mechanisms of action, including the inhibition of hepatitis B surface antigen release, targeting antifibrotic mechanism, and immunomodulation through novel interferons and therapeutic vaccines. The clinical application of potential new vaccines and therapies would enhance the prevention of HBV infection and treatment of chronic hepatitis B. © 2012 by Lippincott Williams & Wilkins.postprin

Do statins reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis B?

In subjects with chronic hepatitis B (CHB), the lifetime risk of developing hepatocellular carcinoma (HCC) is estimated to be 25-37 times compared to non-infected subjects. The process of hepatocarcinogenesis is complex and involves well-documented host, viral, and environmental risk factors. The most important risks include host factors such as older age, male gender, the presence of cirrhosis, and viral factors such as the viral load, genotype, and the presence of basal core promoter mutations. To date, antiviral therapy is the only intervention demonstrated to significantly reduce the risk of HCC development in CHB patients. Although oxidative stress has been implicated in cancer development, there is no established benefit shown from treatment with antioxidizing agents such as silymarin, green tea, and vitamin E.published_or_final_versio

Levels of HBV DNA and not HBsAg are associated with biochemical flares after HBeAg seroconversion

BACKGROUND: The role of HBsAg levels in predicting subsequent flares in chronic hepatitis B patients after HBeAg seroconversion is not known METHODS: Serum HBsAg and HBV DNA levels were determined in 224 CHB patients at 6-12 months after spontaneous HBeAg seroconversion. Serum HBV DNA levels were performed using Cobas Taqman assay. HBsAg titers were determined using Roche Elecsys HBsAg II ...postprin

Effect of nucleos(t)ide analogues therapy on HBsAg, intrahepatic HBV DNA and covalently closed circular DNA levels

BACKGROUND: We aimed to study 1) the effects of 1-year nucleos(t)ide analogue (NA) therapy on HBsAg and covalently closed circular DNA (cccDNA) levels; and 2) the possible use of HBsAg reduction as a marker for cccDNA reduction. METHODS: We recruited 124 NA-treated patients with ...postprin

Clinicopathological study of renal biopsies after liver transplantation

published_or_final_versio

Chronic hepatitis B - New goals, new treatment

published_or_final_versio

A new model using routinely available clinical parameters to predict significant liver fibrosis in chronic hepatitis B

Objective: We developed a predictive model for significant fibrosis in chronic hepatitis B (CHB) based on routinely available clinical parameters. Methods: 237 treatment-naïve CHB patients [58.4% hepatitis B e antigen (HBeAg)-positive] who had undergone liver biopsy were randomly divided into two cohorts: training group (n = 108) and validation group (n = 129). Liver histology was assessed for fibrosis. All common demographics, viral serology, viral load and liver biochemistry were analyzed. Results: Based on 12 available clinical parameters (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP, GGT and AFP), a model to predict significant liver fibrosis (Ishak fibrosis score ≥3) was derived using the five best parameters (age, ALP, AST, AFP and platelet). Using the formula log(index+1) = 0.025+0.0031(age)+0.1483 log(ALP)+0.004 log(AST)+0.0908 log(AFP+1)-0.028 log(platelet), the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index predicts significant fibrosis with an area under the receiving operating characteristics (AUROC) curve of 0.776 [0.797 for patients with ALT <2×upper limit of normal (ULN)] The negative predictive value to exclude significant fibrosis was 88.4%. This predictive power is superior to other non-invasive models using common parameters, including the AST/platelet/GGT/AFP (APGA) index, AST/platelet ratio index (APRI), and the FIB-4 index (AUROC of 0.757, 0.708 and 0.723 respectively). Using the PAPAS index, 67.5% of liver biopsies for patients being considered for treatment with ALT <2×ULN could be avoided. Conclusion: The PAPAS index can predict and exclude significant fibrosis, and may reduce the need for liver biopsy in CHB patients. © 2011 Seto et al.published_or_final_versio

High hepatitis B surface antigen levels predict insignificant fibrosis in hepatitis B e antigen positive chronic hepatitis B

INTRODUCTION: There is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB). METHODS: Serum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation. RESULTS: 140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT 1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p/= 25,000 IU/mL was independently associated with fibrosis score </= 1 (p=0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT </=2xULN, positive and negative predictive values for predicting fibrosis score </= 1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology. CONCLUSION: Among HBeAg-positive patients with ALT </=2xULN, high serum HBsAg levels can accurately predict fibrosis score </= 1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.published_or_final_versio