Novel genetic variants of Hepatitis B Virus in fulminant hepatitis

• Main Authors: Chook, Jack Bee *, Ngeow, Yun Fong, Tee, Kok Keng, Peh, Suat Cheng *, Mohamed, Rosmawati
• Format: Article
• Language: English
• Published: Hindawi 2017
• Subjects: R Medicine (General)
• Online Access: http://eprints.sunway.edu.my/871/1/Chook%20JB%202017%20Novel%20Genetic%20variants%20of%20fulminant%20HBV%20J%20Pathog.pdf; http://eprints.sunway.edu.my/871/; http://doi.org/10.1155/2017/1231204
• Institution: Sunway University

Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%),K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%).We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH.