Pre-s mutation is a significant risk factor for hepatocellular carcinoma development: a long-term retrospective cohort study.
BACKGROUND
Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC).


OBJECTIVE
We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way.


METHODS
A total of 195 patients with chronic HBV infection [age: 43.7 ± 10.8 years, males: 141 (72.3 %), genotype C: 195 (100 %), hepatitis B e antigen (HBeAg) positive: 109 (55.9 %), cirrhosis: 79 (40.5 %), and pre-S mutation positive: 44 (22.6 %)] were followed up for a median of 7.2 years (range 1.0-7.8 years).


RESULTS
HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4 %, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7 %, p < 0.001) and showed higher hazard ratio for HCC [3.04 (95 % CI 1.24-7.42), p = 0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged ≥50 years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3 %), compared to those without (16.1 %, p < 0.001).


CONCLUSIONS
Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development.
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.
Dong Hyun
DH
Sinn
Moon Seok
MS
Choi
Geum-Youn
GY
Gwak
Yong-Han
YH
Paik
Joon Hyeok
JH
Lee
Kwang Cheol
KC
Koh
Seung Woon
SW
Paik
Byung Chul
BC
Yoo
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics / Q000821:virology; D015331:Cohort Studies; D005260:Female; D015967:Gene Expression Regulation, Viral; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors
D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050807:presurface protein 2, hepatitis B surface antigen