Natural history of chronic hepatitis B: what exactly has REVEAL Revealed?

Abstract

Chronic hepatitis B virus (HBV) infection is a serious public health problem because of its worldwide prevalence and potential to cause adverse consequences. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study carried out in Taiwan was used to investigate the natural history of chronic hepatitis B. The REVEAL-HBV study has established an HBV viral load paradigm in the natural history of chronic hepatitis B (CHB). Serum HBV DNA level has been shown to be significantly and independently associated with incidence of hepatocellular carcinoma (HCC) and cirrhosis and liver-related mortality across a biological gradient. It is also a major predictor of HBsAg seroclearance. Genetic features including HBV genotype and basal core promoter A1762T/G1764A mutant, and precore G1896A mutant were documented as predictors of HCC risk. Inactive HBV carriers still had an increased risk on HCC development and liver-related mortality compared with HBsAg -seronegatives. Nomograms focusing on facilitating risk communication between patients and clinicians were developed incorporating non-invasive clinical parameters to predict long-term HCC risk. These will hopefully contribute to evidence-based decisions in the clinical management of CHB patients. A somewhat provocative and novel finding from the REVEAL-HBV study is the association of chronic HBV infection in active replication with an increased pancreatic cancer risk especially in women less than 50 years old. This finding will hopefully spur further research in this area seeking confirmatory evidence. Finally, we hope that the REVEAL-HBV study will continue to be a source of data to answer other important questions in chronic hepatitis B research going forward. Background and overview

IL6 gene allele-specific C/EBPα-binding activity affects the development of HBV infection through modulation of Th17/Treg balance

“…Serum ALT level reflects interaction between host and virus, and has been recognized as a risk predictor to cirrhosis and HCC in patients with CHB. 42 Thus, IL6 gene polymorphism may be associated with disease progress to cirrhosis and HCC in CHB infection, and further study is warranted to clarify this hypothesis.…”

Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B–Related Hepatocellular Carcinoma

“…Alcohol consumption has been previously established as a risk factor for hepatocellular carcinoma even among individuals with chronic HBV infection (6,7,15,16). In one landmark study, chronically infected individuals who consumed alcohol had an adjusted HR (95% CI) of 1.6 (1.1-2.4) of developing hepatocellular carcinoma compared with those who did not consume alcohol even after adjustment for other strongly predictive factors, such as HBV DNA levels, alanine transaminase (ALT) levels, HBeAg serostatus, and liver cirrhosis (6).…”

Factors Associated with Non-Adherence to HBV Antiviral Therapy

“…HBV anti-viral therapy has the potential to reduce the burden of HBV-related liver disease [1] by suppressing HBV deoxyribonucleic acid (DNA) replication to undetectable levels, reducing the progression of liver fibrosis [4] and reducing the risk of hepatocellular carcinoma HCC development [4,5].…”