BACKGROUND & AIMS: We assessed the influence of genetic variants in the hepatitis B virus (HBV) core, which is a principal immunologic target, on the progression to hepatocellular carcinoma (HCC) in a cohort of 4841 male HBV carriers followed up for 16 years. METHODS: First, baseline sera from 116 HCC cases and 154 controls nested within the cohort were used for sequencing of the HBV core gene to screen for variants with effects on HCC progression. By applying a high-throughput assay for detecting viral single nucleotide substitutions, we then used a longitudinal study (n = 1143) to examine whether 2 identified variants that lie in the region within or flanking epitopes affected the natural course of hepatitis B through investigating their relationships with time trends for viral load and clinical features. RESULTS: In the nested case-control study, there were 6 core variants associated with decreased risk of HCC after accounting for viral genotype; 5 lie in the region within or flanking epitopes (P < .04). Each variant correlated with a 0.7- to 1-log decrease in viral load and hepatitis B virus e antigen negativity at baseline. The longitudinal study further showed that the appearance of 2 such variants (T1938C and T2045A) was preceded by long-term diminished viral load and decreased rate of liver abnormalities and was significantly less frequent in individuals with a prolonged immune clearance phase that associated with spectrum of liver disease than those in inactive carrier or reactivation phase. CONCLUSIONS: HBV core variants affecting the kinetics of host-virus interplay may influence longitudinal viral load and HCC progression.
BACKGROUND & AIMS: We assessed the influence of genetic variants in the hepatitis B virus (HBV) core, which is a principal immunologic target, on the progression to hepatocellular carcinoma (HCC) in a cohort of 4841 male HBV carriers followed up for 16 years. METHODS: First, baseline sera from 116 HCC cases and 154 controls nested within the cohort were used for sequencing of the HBV core gene to screen for variants with effects on HCC progression. By applying a high-throughput assay for detecting viral single nucleotide substitutions, we then used a longitudinal study (n = 1143) to examine whether 2 identified variants that lie in the region within or flanking epitopes affected the natural course of hepatitis B through investigating their relationships with time trends for viral load and clinical features. RESULTS: In the nested case-control study, there were 6 core variants associated with decreased risk of HCC after accounting for viral genotype; 5 lie in the region within or flanking epitopes (P < .04). Each variant correlated with a 0.7- to 1-log decrease in viral load and hepatitis B virus e antigen negativity at baseline. The longitudinal study further showed that the appearance of 2 such variants (T1938C and T2045A) was preceded by long-term diminished viral load and decreased rate of liver abnormalities and was significantly less frequent in individuals with a prolonged immune clearance phase that associated with spectrum of liver disease than those in inactive carrier or reactivation phase. CONCLUSIONS:HBV core variants affecting the kinetics of host-virus interplay may influence longitudinal viral load and HCC progression.
Authors: Peter A Revill; Thomas Tu; Hans J Netter; Lilly K W Yuen; Stephen A Locarnini; Margaret Littlejohn Journal: Nat Rev Gastroenterol Hepatol Date: 2020-05-28 Impact factor: 46.802
Authors: Maria Homs; Maria Buti; David Tabernero; Josep Quer; Alex Sanchez; Noelia Corral; Rafael Esteban; Francisco Rodriguez-Frias Journal: World J Gastroenterol Date: 2012-11-14 Impact factor: 5.742
Authors: Q Wang; M I Fiel; S Blank; W Luan; H Kadri; K W Kim; F Manizate; A G Rosenblatt; D M Labow; M E Schwartz; S P Hiotis Journal: Br J Cancer Date: 2013-07-11 Impact factor: 7.640