Journal List > Ann Clin Microbiol > v.16(2) > 1078492

Kim, Lee, and Lee: Association between Apolipoprotein E Genotype and Treatment Response in Chronic Hepatitis C

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.

Conclusion

There was no significant effect of the ApoE genotype on the clinical aspects of HCV infection and the antiviral response, including SVR, EVR and ETR, in chronic HCV hepatitis patients.

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Table 1.
ApoE genotypes of study subjects
HCV genotype 1 HCV genotype non-1 P* All patients Controls [17] P*
ApoE genotypes, n (%)            
  E2/E2 0 (0.0) 0 (0.0)   0 (0.0) 0 (0.0)  
  E2/E3 7 (7.0) 3 (4.6)   13 (6.6) 20 (10.4)  
  E2/E4 1 (1.0) 1 (1.5)   2 (1.0) 1 (0.5)  
  E3/E3 77 (77.8) 50 (76.9) NS 152 (77.6) 147 (76.6) NS
  E3/E4 14 (14.2) 11 (16.9)   28 (14.3) 24 (12.5)  
  E4/E4 0 (0.0) 0 (0.0)   1 (0.5) 0 (0.0)  
Total 99 (100) 65 (100)   196 (100) 192 (100)  

Pearson χ2 test.

Abbreviation: NS, not significant.

Table 2.
Clinical findings of study subjects at the time of initial diagnosis
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§

Mean±SD;

Comparison of HCV genotype 1 versus HCV genotype non-1 using the Student t-test;

Positive number/N;

§ Comparison of HCV genotype 1 versus HCV genotype non-1 using the Pearson χ2 test.

Abbreviations: SVR, sustained virologic response; EVR, early virologic response; ETR, end of treatment response; NS, not significant.

Table 3.
Relationship between ApoE genotypes and clinical findings
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

Mean±SD;

Mann-Whitney U test;

Positive number/N;

§ Pearson χ2 test.

Abbreviation: NS, not significant.

Table 4.
Viral response rates to antiviral therapy in chronic HCV infection according to ApoE genotype
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

Pearson χ2 test.

Abbreviations: SVR, sustained virologic response; EVR, early virologic response; ETR, end of treatment response; NS, not significant.

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