Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website http://www.gastrores.org

Original Article

Volume 8, Number 6, December 2015, pages 281-290


Hepatitis C in Liver Allograft Recipients: Utility of One-Year Post-Transplantation Biopsy as an Indicator of Antiviral Therapy

Figures

Figure 1.
Figure 1. Distribution of patients in study cohort.
Figure 2.
Figure 2. Graft survival rate in SVR and viremic patients categorized according to fibrosis stage at 1 year post-transplant. There is a trend of worsening graft failure from stage 0 to stage 5.
Figure 3.
Figure 3. Cumulative graft survival among patients alive at 1 year post-transplant; Kaplan-Meier analysis, comparison by log-rank test.
Figure 4.
Figure 4. Cumulative patient survival among patients alive at 1 year post-transplant; Kaplan-Meier analysis, comparison by log-rank test.
Figure 5.
Figure 5. Cumulative graft survival according to fibrosis stage (at 1 year post-transplant) and treatment response; Kaplan-Meier analysis, comparison by log-rank test; mean survival with confidence intervals shown. Std. error: standard error.

Tables

Table 1. Demographics and Baseline Clinical Features
 
Mild disease (n = 116)Severe disease (n = 136)P value
All values are shown as mean ± SD or proportion as appropriate. Comparison by two-tailed t-test or Chi-square test as appropriate. n: number. SD: standard deviation.
Age (years)52 ± 751 ± 60.06
Gender (male)98 (84%)96 (71%)0.009
Caucasian107 (92%)124 (91%)0.76
Child-Pugh status0.14
  Class A12 (10%)6 (4%)
  Class B69 (59%)80 (59%)
  Class C35 (30%)50 (37%)
Child-Pugh score9 ± 1.89 ± 1.60.12
MELD score16 ± 716 ± 80.87
Blood group0.62
  A40 (34%)56 (41%)
  B11 (9%)14 (10%)
  AB9 (8%)7 (5%)
  O56 (48%)59 (43%)
Co-morbidities
  Diabetes mellitus35 (30%)37 (27%)0.60
  Hypertension43 (37%)43 (32%)0.36
  BMI (kg/m2)29 ± 528 ± 50.12
  Obesity (BMI ≥ 30)44 (38%)43 (32%)0.29
  Renal Failure16 (14%)22 (16%)0.60
  Hepatocellular carcinoma32 (28%)37 (27%)0.95

 

Table 2. Baseline Laboratory Features
 
Mild disease (n = 116)Severe disease (n = 136)P value
All values are shown as mean ± SD or proportion as appropriate. Comparison by two-tailed t-test or Chi-square test as appropriate. *n = 209. **n = 238; data unavailable in 14 patients (mild disease: 5, severe disease: 9). ***Cytomegalovirus antibody (positive: > 4 IU/L). ****Epstein-Barr viral capsid antigen antibody (positive: > 20 IU/L); n = 243. n: number. SD: standard deviation; IU: international units.
Hemoglobin (g/dL)12.0 ± 2.111.7 ± 2.10.20
WBC (× 103/L)5.0 ± 2.75.9 ± 4.00.04
Platelets (× 103/L)67 ± 4074 ± 500.25
Bilirubin (mg/dL)4.1 ± 6.24.6 ± 7.40.55
ALT (IU/L)131 ± 411152 ± 4200.69
AST (IU/L)334 ± 1926255 ± 9140.67
ALP (IU/L)166 ± 106164 ± 880.87
γGTP (IU/L)97 ± 11695 ± 970.89
Albumin (g/dL)2.9 ± 0.52.8 ± 0.60.29
INR1.4 ± 0.41.4 ± 0.50.95
Creatinine (mg/dL)1.3 ± 1.31.4 ± 1.40.77
HCV RNA (× 106 IU/mL)*1.02 ± 3.42.0 ± 6.40.16
HCV genotype 1**89 (81%)111 (87%)0.22
Anti-CMV, IgG (IU/L)105 ± 122102 ± 1260.86
Anti-CMV, IgG-positive***81 (70%)81 (60%)0.09
Anti-EBV, IgG (IU/L)251 ± 222242 ± 1960.75
Anti-EBV, IgG-positive****79 (71%)101 (77%)0.24

 

Table 3. Donor Features
 
Mild disease (n = 116)Severe disease (n = 136)P value
All values are shown as mean ± SD or proportion as appropriate. Comparison by two-tailed t-test or Chi-square test as appropriate. *n = 247. **n = 243. ***n = 245. n: number. SD: standard deviation; anti-HCV: antibody to hepatitis C virus; anti-HBc: antibody to hepatitis B core antigen; CMV: cytomegalovirus.
Age (years)41 ± 1745 ± 160.026
Males68 (59%)78 (57%)0.84
Caucasian96 (83%)120 (88%)0.21
Living donor9 (8%)14 (10%)0.49
Anti-HCV positive*13 (11%)22 (17%)0.25
Anti-HBc positive**13 (12%)14 (11%)0.86
Anti-CMV IgG positive***70 (63%)82 (61%)0.76
Donor biopsy61 (53%)82 (60%)0.22
Blood group0.83
  A39 (34%)52 (38%)
  B13 (11%)13 (10%)
  AB7 (6%)6 (4%)
  O57 (49%)65 (48%)
Donor recipient mismatch
  Gender48 (41%)58 (43%)0.84
  Racial24 (21%)26 (19%)0.75
  ABO blood group5 (4%)7 (5%)0.76

 

Table 4. Operative Features
 
Mild disease (n = 116)Severe disease (n = 136)P value
All values are shown as mean ± SD or proportion as appropriate. Comparison by two-tailed t-test or Chi-square test as appropriate. *n = 246. n: number. SD: standard deviation.
Cold ischemia time (h)9.8 ± 3.49.9 ± 3.90.82
Warm ischemia time (min)34 ± 1133 ± 100.24
Red cell transfusion (unit)*7.5 ± 6.78.5 ± 7.50.28
Platelets (unit)6.2 ± 8.17.7 ± 9.40.20
Fresh frozen plasma (unit)*6.4 ± 6.67.6 ± 7.30.20
Piggyback graft placement98 (84%)117 (86%)0.73
Duct-duct anastomosis110 (95%)129 (95%)1.0
T-tube placement77 (66%)96 (71%)0.47
Veno-venous bypass81 (70%)94 (69%)0.90
Length of stay post-transplant (days)19 ± 1921 ± 230.64

 

Table 5. Immunosuppression and Antiviral Therapy
 
Mild disease (n = 116)Severe disease (n = 136)P value
All values are shown as mean ± SD or proportion as appropriate. Comparison by two-tailed t-test or Chi-square test as appropriate. n: number. SD: standard deviation. *Perioperative with either antithymocyte globulin or alemtuzumab. **During the first post-operative year and hydrocortisone equivalent. ***Post-transplant treatment with pegylated interferon-α2b or pegylated interferon-α2a with ribavirin.
Corticosteroids107 (92%)121 (89%)0.38
Anti-T cell antibody*10 (9%)27 (20%)0.012
Mycophenolate mofetil29 (25%)33 (24%)0.89
Sirolimus1 (1%)4 (3%)0.24
Acute rejection33 (28%)60 (44%)0.01
Acute rejection episodes0.4 ± 0.70.6 ± 0.80.034
ACR: steroid boluses29 (25%)50 (37%)0.045
Chronic rejection4 (3%)9 (7%)0.26
Cumulative steroid dose (g)**154 ± 780214 ± 7810.54
Cumulative tacrolimus dose (mg/year)467 ± 577686 ± 9960.038
Interferon therapy***79 (68%)99 (73%)0.41
Interferon responders28 (24%)31 (23%)0.8

 

Table 6. Predictors of Disease Severity at 1 Year Post-Transplant
 
Variables includedB ± SEOdds ratio95% CIP value
Logistic regression analysis. R2 = 0.07 (Hosmer & Lemeshow), 0.09 (Cox & Snell), 0.12 (Nagelkerke). Model χ2 =24.1, P < 0.001. B: coefficient of regression. SE: standard error; CI: confidence interval.
Recipient age-0.055 ± 0.020.950.91 - 0.980.007
Female gender0.96 ± 0.342.61.33 - 5.070.005
Donor age0.02 ± 0.011.021.0 - 1.040.021
Anti-T cell antibody0.85 ± 0.410.430.19 - 0.950.037
Constant2.7 ± 1.1214.880.016

 

Table 7. Prediction of Graft Failure Beyond First Post-Transplant Year
 
VariableB ± SEHazard ratioP value
Cox proportional hazards analysis. B: coefficient of regression. SE: standard error.
Fibrosis stage 5/61.24 ± 0.513.460.016
Fibrosis stage 3/40.81 ± 0.322.250.011
Fibrosis stage 20.54 ± 0.361.710.133
Recipient age0.01 ± 0.021.010.649
Female gender-0.13 ± 0.320.880.690
Donor age0.03 ± 0.011.030.0007
Anti-T cell antibody0.32 ± 0.301.380.285

 

Table 8. Allograft Failure Risk Based on Treatment Status
 
P valueHR95.0% CI HR
LowerUpper
CI: confidence interval; HR: hazard ratio.
Mild disease viremic0.001
Mild disease SVR0.0260.1030.0140.761
Severe disease viremic0.0072.0501.2183.451
Severe disease SVR0.4190.7210.3261.594