Difference in quasispecies of the hypervariable region 1 of hepatitis C virus between alcoholic and non-alcoholic patients.
BACKGROUND
Habitual alcohol intake is known to aggravate the clinical outcome of hepatitis C virus (HCV)-related chronic liver diseases and to increase the risk of hepatocellular carcinoma.


METHODS
To investigate the possible mechanism of these effects by alcohol, we examined 31 cases of HCV-related chronic liver diseases of which 17 cases were drinking just before admission and the remaining 14 cases were non-drinkers. The studied cases included 18 patients with chronic hepatitis, six with liver cirrhosis and seven with hepatocellular carcinoma. The quasispecies of the hypervariable region 1 of the HCV genome were analyzed by using polymerase chain reaction single strand conformation polymorphism (PCR-SSCP). Hepatitis C virus viral load was quantitated by using multicyclic PCR after reverse transcription of the 5' non-coding region of the genome.


RESULTS
The mean PCR-SSCP band number that reflected the quasispecies complexity in hypervariable region 1 was more significantly increased in alcoholics than in non-alcoholics (5.5 +/- 1.4 vs 3.9 +/- 1.1, P< 0.01). The significant increase in alcoholics remained, even if the cases were restricted to males (P < 0.01), to HCV genotype 1b (P < 0.05) or to chronic hepatitis (P < 0.05). The HCV viral load was not statistically different between alcoholic and non-alcoholic HCV-related chronic liver diseases (5.02 x 10(6) +/- 5.16 x 10(6) copies/mL vs 9.00 x 10(7) +/- 2.75 x 10(8) copies/mL, P = 0.28). Mutation events seemed to occur randomly when amino acid sequences of hypervariable region 1 were compared between four drinkers and four non-drinkers.


CONCLUSIONS
The enhanced quasispecies complexity in hypervariable region 1 of HCV in alcoholics may be the main cause of more progressive HCV-related chronic liver diseases, and may provide the disease the resistance against any therapeutic modalities including interferon.
Takahashi
K
K
Third Department of Internal Medicine, Niigata University School of Medicine, Japan. torutoru@med.niigata-u.ac.jp
Takahashi
T
T
Takahashi
S
S
Watanabe
K
K
Boku
S
S
Matsui
S
S
Arai
F
F
Asakura
H
H
D000368:Aged; D000437:Alcoholism / Q000150:complications* / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007135:Immunoglobulin Variable Region; D008107:Liver Diseases / Q000235:genetics* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012016:Reference Values
D007135:Immunoglobulin Variable Region