Abstract:
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.
journal_name
J Gastroenterol Hepatoljournal_title
Journal of gastroenterology and hepatologyauthors
Takahashi K,Takahashi T,Takahashi S,Watanabe K,Boku S,Matsui S,Arai F,Asakura Hdoi
10.1046/j.1440-1746.2001.02462.xsubject
Has Abstractpub_date
2001-04-01 00:00:00pages
416-23issue
4eissn
0815-9319issn
1440-1746journal_volume
16pub_type
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