초록
Background
Hepatitis C virus (HCV) causes a chronic infection, resulting in progressive liver damage. Recent studies have described the protective effect of the apolipoprotein E (ApoE) genotype on liver damage in cases of HCV infection. Their findings were explained by the influence of the ApoE genotype on HCV pathology, which seems to be integrally linked to the process of HCV uptake into hepatocytes. We investigated whether specific ApoE genotypes were associated with the different clinical aspects of HCV infection in patients with chronic HCV.
Methods
From the whole blood of 196 chronic HCV hepatitis patients, the ApoE genotypes were determined by an allele-specific polymerase chain reaction. Several markers, including liver enzymes, platelet counts and HCV viral loads, as well as the radio-logic findings, were investigated. In order to estimate the treatment outcome, the sustained virologic response (SVR), early virologic response (EVR) and end-of-treatment response (ETR) were determined according to the HCV viral loads.
Results
Based on genotyping, 15.8% (n=31) of the patients had the ApoE E4 allele (E2/E4, E3/E4, E4/E4), while 84.2% (n=165) were missing the ApoE E4 allele (E2/E2, E2/E3, E3/E3). Several clinical results of the E4-positive group, including liver enzymes, albumin, platelet counts, HCV viral loads and hepatic coarseness were not significantly different from those of E4-negative group. There were no differences in the SVR, EVR and ETR between patients with the ApoE E4 allele and those without the ApoE E4 allele.
REFERENCES
2.Kim YS., Pai CH., Chi HS., Kim DW., Min YI., Ahn YO. Prevalence of hepatitis C virus antibody among Korean adults. J Korean Med Sci. 1992. 7:333–6.
3.Kim YJ. The management of chronic hepatitis C. Korean J Med. 2009. 77:275–81.
4.The Korean Association for the Study of the Liver. Practice guideline for management of hepatitis C. Korean J Hepatol. 2004. 10(Suppl):S101–5.
5.Poynard T., Bedossa P., Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997. 349:825–32.
6.Sud A., Hui JM., Farrell GC., Bandara P., Kench JG., Fung C, et al. Improved prediction of fibrosis in chronic hepatitis C using measures of insulin resistance in a probability index. Hepatology. 2004. 39:1239–47.
7.McCaughan GW., George J. Fibrosis progression in chronic hepatitis C virus infection. Gut. 2004. 53:318–21.
8.Agnello V., Abel G., Elfahal M., Knight GB., Zhang QX. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A. 1999. 96:12766–71.
9.Serfaty L., Andreani T., Giral P., Carbonell N., Chazouillères O., Poupon R. Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C. J Hepatol. 2001. 34:428–34.
10.Kuhlmann I., Minihane AM., Huebbe P., Nebel A., Rimbach G. Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review. Lipids Health Dis. 2010. 9:8.
11.Wozniak MA., Itzhaki RF., Faragher EB., James MW., Ryder SD., Irving WL. Trent HCV Study Group. Apolipoprotein E-epsilon 4 protects against severe liver disease caused by hepatitis C virus. Hepatology. 2002. 36:456–63.
12.Mueller T., Gessner R., Sarrazin C., Graf C., Halangk J., Witt H, et al. Apolipoprotein E4 allele is associated with poor treatment response in hepatitis C virus (HCV) genotype 1. Hepatology. 2003. 38:1592; author reply 1592-3.
13.Price DA., Bassendine MF., Norris SM., Golding C., Toms GL., Schmid ML, et al. Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus infection. Gut. 2006. 55:715–8.
14.Ryu HG., Kwon OD. Apolipoprotein E epsilon 4 allele is not associated with age at onset or MMSE of Parkinson's disease in a Korean study. Parkinsonism Relat Disord. 2010. 16:615–7.
15.Davignon J., Gregg RE., Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988. 8:1–21.
16.Robertson FW., Cumming AM. Effects of apoprotein E polymorphism on serum lipoprotein concentration. Arteriosclerosis. 1985. 5:283–92.
17.Kono Y., Hayashida K., Tanaka H., Ishibashi H., Harada M. High- density lipoprotein binding rate differs greatly between genotypes 1b and 2a/2b of hepatitis C virus. J Med Virol. 2003. 70:42–8.
Table 1.
Table 2.
All patients (N) | HCV genotype 1 (N) | HCV genotype non-1 (N) | P | |
---|---|---|---|---|
Age (year)∗ | 58.8±11.6 (196) | 57.3±11.6 (99) | 58.7±11.5 (65) | NS† |
Sex | ||||
Male | 57.1% (112/196)‡ | 62.6% (62/99)‡ | 46.2% (30/65)‡ | <0.05§ |
Female | 42.9% (84/196)‡ | 37.4% (37/99)‡ | 53.8% (35/65)‡ | |
Radiologic findings | ||||
Coarse echotexture | 48.0% (94/153)‡ | 68.8% (53/77)‡ | 55.6% (30/54)‡ | NS§ |
Fatty liver | 33.2% (65/153)‡ | 44.2% (34/77)‡ | 44.4% (24/54)‡ | NS§ |
Laboratory findings | ||||
AST (U/L)∗ | 71.7±60.1 (193) | 72.9±53.9 (96) | 73.9±61.6 (65) | NS† |
ALT (U/L)∗ | 77.2±82.6 (195) | 84.2±78.3 (98) | 77.9±98.5 (65) | NS† |
Albumin (mg/dL)∗ | 4.19±0.51 (188) | 4.23±0.53 (95) | 4.22±0.44 (64) | NS† |
Cholesterol (mg/dL)∗ | 161.5±31.0 (163) | 163.6±30.3 (82) | 162.3±27.9 (58) | NS† |
Platelet count (103/μ L)∗ | 175.8±71.9 (185) | 175.4±72.9 (92) | 184.8±71.8 (63) | NS† |
Prothrombin time (%)∗ | 90.7±14.6 (120) | 90.2±14.1 (65) | 91.3±14.9 (35) | NS† |
HCV RNA (106 IU/mL)∗ | 3.72±6.30 (167) | 5.22±7.60 (94) | 1.78±3.37 (62) | <0.05† |
Virologic response | ||||
SVR | 48.9% (65/133)‡ | 40.9% (27/66)‡ | 68.1% (32/47)‡ | <0.05§ |
EVR | 60.4% (84/139)‡ | 62.0% (49/79)‡ | 72.7% (32/44)‡ | NS§ |
ETR | 57.7% (75/130)‡ | 58.0% (40/69)‡ | 71.1% (32/45)‡ | NS§ |
Table 3.
All patients | HCV genotype 1 | HCV genotype non-1 | |||||||
---|---|---|---|---|---|---|---|---|---|
E4 negative (N) | E4 positive (N) | P | E4 negative (N) | E4 positive (N) | P | E4 negative (N) | E4 positive (N) | P | |
Age (year)∗ | 58.5±11.4 (165) | 60.3±12.6 (31) | NS† | 56.7±11.3 (84) | 60.4±13.4 (15) | NS† | 58.3±11.5 (53) | 60.3±11.6 (12) | NS† |
Sex | |||||||||
Male | 57.6% (95/165)‡ | 54.8% (17/31)‡ | NS§ | 63.1% (53/84)‡ | 60.0% (9/15)‡ | NS§ | 56.6% (30/53)‡ | 41.7% (5/12)‡ | NS§ |
Female | 42.4% (70/165)‡ | 45.2% (14/31)‡ | NS§ | 36.9% (31/84)‡ | 40.0% (6/15)‡ | NS§ | 43.4% (23/53)‡ | 58.3% (7/12)‡ | NS§ |
Radiologic findings | |||||||||
Coarse echotexture | 49.7% (82/130)‡ | 38.7% (12/23)‡ | NS§ | 70.8% (46/65)‡ | 58.3% (7/12)‡ | NS§ | 58.7% (27/46)‡ | 37.5% (3/8)‡ | NS§ |
Fatty liver | 32.7% (54/130)‡ | 35.5% (11/23)‡ | NS§ | 41.5% (27/65)‡ | 58.3% (7/12)‡ | NS§ | 43.5% (20/46)‡ | 50% (7/12)‡ | NS§ |
Laboratory findings | |||||||||
AST (U/L)∗ | 72.9±63.9 (162) | 65.5±34.0 (31) | NS† | 73.7±57.1 (81) | 68.7±32.6 (15) | NS† | 74.8±65.9 (53) | 70.0±38.6 (12) | NS† |
ALT (U/L)∗ | 77.4±87.8 (164) | 76.3±47.4 (31) | NS† | 84.7±83.0 (83) | 81.5±46.0 (15) | NS† | 77.3±106.5 (53) | 80.5±53.8 (12) | NS† |
Albumin (mg/dL)∗ | 4.17±0.53 (157) | 4.30±0.44 (31) | NS† | 4.21±0.54 (80) | 4.37±0.44 (15) | NS† | 4.21±0.45 (52) | 4.26±0.40 (12) | NS† |
Cholesterol (mg/dL)∗ | 160.8±31.8 (137) | 165.0±26.9 (26) | NS† | 164.3±30.8 (69) | 159.5±28.0 (13) | NS† | 160.6±28.9 (49) | 171.4±21.0 (9) | NS† |
Platelet count (103/μ L)∗ | 175.0±73.0 (156) | 177.7±68.0 (29) | NS† | 174.1±72.8 (78) | 182.4±75.9 (14) | NS† | 185.6±73.1 (52) | 180.9±68.4 (11) | NS† |
Prothrombin time (%)∗ | 90.1±15.2 (99) | 93.6±10.9 (21) | NS† | 90.1±14.1 (55) | 90.9±14.6 (10) | NS† | 90.3±16.4 (28) | 95.4±6.1 (7) | NS† |
HCV RNA (106 IU/mL)∗ | 3.93±6.63 (140) | 2.62±4.12 (27) | NS† | 5.46±7.93 (80) | 3.87±5.38 (14) | NS† | 1.93±3.67 (51) | 1.10±1.03 (11) | NS† |
Table 4.
All patients | HCV genotype 1 | HCV genotype non-1 | |||||||
---|---|---|---|---|---|---|---|---|---|
E4 negative | E4 positive | P∗ | E4 negative | E4 positive | P∗ | E4 negative | E4 positive | P∗ | |
SVR | 47.7% (53/111) | 54.5% (12/22) | NS | 41.8% (23/55) | 36.4% (4/11) | NS | 65.0% (26/40) | 85.7% (6/7) | NS |
EVR | 60.0% (72/120) | 63.2% (12/19) | NS | 61.2% (41/67) | 66.7% (8/12) | NS | 71.8% (28/39) | 80.0% (4/5) | NS |
ETR | 58.4% (66/113) | 52.9% (9/17) | NS | 59.3% (35/59) | 50.0% (5/10) | NS | 70.0% (28/40) | 80.0% (4/5) | NS |