Alanine aminotransferase flare-up in hepatitis C virus carriers with persistently normal alanine aminotransferase levels in a hyperendemic area of Japan.
BACKGROUND
The clinical features of hepatitis C virus (HCV) carriers with persistently normal alanine aminotransferase (PNALT) levels (ALT < or = 34 IU/l) have not been fully elucidated. We investigated clinical factors associated with ALT flare-up in PNALT individuals in a HCV hyperendemic area of Japan.


METHODS
We analyzed 101 HCV carriers who had PNALT between 1993 and 2000. The first occurrence of ALT flare-up (ALT > or = 35 IU/l) between 2001 and 2005 was evaluated by the Kaplan-Meier method. Multivariate analysis of factors predicting ALT flare-up were conducted using Cox proportional hazards models.


RESULTS
The mean follow-up period was 2.8 years, and the 5-year cumulative incidence of ALT flare-up was estimated to be 31.8%. In multivariate analysis, an ALT level of 20-34 IU/l and a high serum ferritin level (> or =90 ng/ml) in the most recently available data up to the year 2000, as well as H63D heterozygosity in the HFE gene, were independently and strongly associated with the incidence of ALT flare-up (Hazard ratios = 5.6, 3.1, and 4.8, respectively). In addition, HFE H63D heterozygosity was significantly associated with higher serum ferritin levels in subjects with PNALT (153.8 + or - 73.3 ng/ml in subjects with the 63HD genotype vs. 89.4 + or - 51.3 ng/ml in subjects with the 63HH genotype, P = 0.043).


CONCLUSIONS
HCV carriers with PNALT in this population were at risk for ALT flare-up. Basal ALT levels, serum ferritin levels, and HFE polymorphism are potentially important predictors of ALT flare-up.
Uto
Hirofumi
H
Digestive Disease and Life-style related Disease, Health Research Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-0056, Japan.
Kurogi
Joji
J
Takahama
Yuka
Y
Kusumoto
Kazunori
K
Hayashi
Katsuhiro
K
Ido
Akio
A
Kohara
Michinori
M
Stuver
Sherri O
SO
Moriuchi
Akihiro
A
Hasegawa
Susumu
S
Oketani
Makoto
M
Tsubouchi
Hirohito
H
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000235:genetics; D019353:Endemic Diseases / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000071020:Hemochromatosis Protein; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D018937:Hepatitis C Antibodies / Q000276:immunology; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000201:enzymology* / Q000453:epidemiology* / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012367:RNA, Viral; D004247:DNA; D000410:Alanine Transaminase
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