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 5, October 2015, pages 237-246


Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment

Figures

Figure 1.
Figure 1. Change of fibrosis in patients. SVR: sustained virological response.
Figure 2.
Figure 2. These graphs plot R2 against delta log time in all treatment groups and control group.
Figure 3.
Figure 3. Plots R2 by treatment type. This shows increasing trend in percentage of R2 for a non-linear cubic model fit from “no treatment” to “SVR treatment”. This indicates favorable improvement in time dependent fibrosis scores, and this was most evident with SVR.
Figure 4.
Figure 4. Graft survival: Kaplan-Meier survival curves.

Tables

Table 1. Literature Review [12-21]
 
AuthorYearCountryNStudy designCGFUPre-treatment fibrosisEffect on fibrosis: SVREffect on fibrosis: NREffect on fibrosis: controlP value
N: number of patients; NS: not significant; *: number of patients evaluated histologically; CG: control group; NR: non-responders; SVR: sustained virological response; FU: follow-up.
Tame et al [15]2013Italy35*ProspectiveN40Metavir 2/4(n = 9)
32% improved, 68% unchanged, 0% worsened
(n = 19)
38% improved, 66% unchanged, 16% worsened
(n = 7)
70% improved, 50% unchanged, 50% worsened
0.05
Belli et al [12]2012Italy69*RCTY36Ishaq-Knodell ≤ 3/6(n = 15)
20% worsening
(n = 21)
47.6% worsening
(n = 36)
50% worsening
0.04
Carrion et al [16]2007Spain81RCTY6Metavir 2/4(n = 18)
50% improved, 50% stable, 0% worse
(n = 36)
6% improved, 36% stable, 58% worse
(n = 27)
4% improved, 26% stable, 70% worse
0.009
Bizollon et al [13]2007France25*ProspectiveY6Unknown(n = 8)
100% improved, 0% stable, 0% worse
(n = 17)
65% improved, 35% stable, 0% worse
(n = 21)
5% improved, 19% stable, 76% worse
Significant; P value not presented
Oton et al [17]2006Spain15*RetrospectiveN6Ishaq-Knodell ≥ 1/6(n = 7)
mean score pre-treatment: 2.4/6,
mean score post-treatment: 2.6/6
(n = 8)
mean score pre-treatment: 2.7/6,
mean score post-treatment: 3.7/6
NS
Fernandez et al [18]2006Spain16*ProspectiveN6Scheuer Fibrosis score(n = 7)
mean score pre-treatment: 1.5/4,
mean score post-treatment: 1.1/4
(n = 9)
mean score pre-treatment: 2.4/6,
mean score post-treatment: 2.8/6
NS
Barenguer et al [19]2009Spain47*RetrospectiveN12HAI fibrosis stage 0 - 4No change and improvement 46%No change and improvement 44%NS
Stravitz et al [21]2004USA23RetrospectiveN23(n = 11)
mean score pre-treatment: 1.9/4,
mean score post-treatment: 1.5/4
(n = 12)
mean score pre-treatment: 2.5/4,
mean score post-treatment: 2.7/4
NS
Abdelmalek et al [20]2004USA26*RetrospectiveN24 - 60Not knownAt year 2 FU, 27% improved, 38% unchanged, 35% worsened, At year 3-5 FU, 67% improved, 13% unchanged, 20% worsened.0.05
Bahra et al [14]2007Germany28ProspectiveN361.8(n = 28)
18% improved, 60% unchanged, 21% worsened.
Mean fibrosis stage at 1, 3 and 5 years: 2.0, 2.1 and 1.4 respectively.
NS

 

Table 2. Clinical Characteristics of Patients Prior to Anti-HCV Therapy
 
FeaturesStudy cohort (n = 167)Control group (n = 27)Treatment group (n = 140)P value
n: number of patients; NHBD: non-heart beating donor; MELD: model for end-stage liver disease; CTP: Child-Turcotte-Pugh.
Patient age, mean ± SD49.4 ± 7.748.6 ± 9.0949.5 ± 7.4NS
Patient ≥ 65, % (n)2.4 (4)3.7 (1)2.1 (3)NS
Gender male, % (n)78.4 (131)74.1 (20)79.3 (111)NS
Race white, % (n)89.8 (150)88.9 (15)90 (126)NS
Non-Hispanic, %95.8 (160)88.9 (24)90 (126)NS
Donor age, mean ± SD40.6 ± 17.341.1 ± 18.840.5 ± 17.1NS
Donor age, % > 5031.7 (53)29.6 (8)32.1 (45)NS
Donor gender, % male55.7 (53)55.6 (15)55.7 (78)NS
Donor ethnic, % white85 (142)81.5 (22)85.7 (120)NS
Donor ethnic, % non-Hispanic83.8 (140)77.8 (21)85 (119)NS
Donor NHBD, % (n)6.3 (4)00(00)7.7 (4)NS
MELD score, mean ± SD16.4 ± 7.118.2 ± 7.916 ± 6.9NS
Child-Pugh score, mean ± SD7.8 ± 1.587.9 ± 1.57.8 ± 1.5NS
Cold ischemia time, h ± SD11.5 ± 3.512.9 ± 3.911.3 ± 3.4NS
Warm ischemia time, min ± SD34.8 ± 21.128.5 ± 24.036 ± 20.4NS
Induction therapy, % (n)16.8 (28)14.8 (4)17.1 (24)NS
Received steroids, % (n)81.6 (129)87 (20)80.7 (109)NS

 

Table 3. Anti-HCV Treatment Course
 
Clinical featuresControl (n = 27)Treatment (n = 140)P value
MeanSDMeanSD
SD: standard deviation; ALT; alanine aminotransferase; AST: aspartate aminotransferase; ALP: alkaline phosphatase; MHAI: modified histologic activity index.
Bilirubin pre-treatment, mg/dL0.910.611.291.92NS
Bilirubin at initiation, mg/dL2.866.071.613.47NS
Bilirubin at follow-up, mg/dL5.499.143.778.53NS
ALT pre-treatment, IU/dL121.56122.8496.89103.40NS
AST pre-treatment, IU/dL99.11115.6190.09130.42NS
AST/ALT pre-treatment0.890.510.920.42NS
ALP pre-treatment, IU/dL275.73311.36171.11190.02NS
Cholestasis index2.292.462.211.95NS
Creatinine pre-treatment, mg/dL1.350.511.260.42NS
Time from transplant to pre-treatment biopsy, years0.991.460.901.05NS
MHAI grade 0 - 18 pre-treatment5.201.864.932.78NS
Fibrosis stage 0 - 6 pre-treatment1.111.311.341.46NS
Time from transplant to treatment, years0.981.06NS
Treatment duration, years1.621.16NS
Time from transplant to follow-up biopsy, years3.292.313.972.89NS

 

Table 4. Fibrosis Analysis
 
Control groupNon-respondersRelapsersSVRP value
LT: liver transplantation.
Time interval between LT and initiation of treatment, years0.891.171.01NS
Time interval between LT and first liver biopsy, years1.030.811.060.96NS
Time interval between LT and second liver biopsy, years3.404.123.472.92NS
Time interval between first and second liver biopsy, years2.373.322.403.00Ns
Mean fibrosis change between two biopsies2.042.111.571.370.08
Mean fibrosis stage change per year1.020.630.650.450.08
Direction of change in fibrosisNS
  Regression, % (n)7.4 (2)7.4 (6)6.2 (2)11.1 (3)
  No change, % (n)18.5 (5)22.2 (18)18.8 (6)18.5 (5)
  Progression, % (n)74.1 (20)70.4 (57)75 (24)70.4 (19)