# Chemokine Receptor-5Δ32 Mutation is No Risk Factor for Ischemic-Type Biliary Lesion in Liver Transplantation

Authors: Christoph Heidenhain; Gero Puhl; Christian Moench; Anja Lautem; Peter Neuhaus
Journal: Journal of Transplantation
 (2009)

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## Abstract

It has been shown that certain chemokine receptor polymorphisms may correspond to certain complications after organ transplantation. Ischemic-type biliary lesion (ITBL) encounters for major morbidity and mortality in liver transplant recipients. So far, the exact cause for ITBL remains unclear. Certain risk factors for the development of ITBL like donor age and cold ischemic time
are well described. In a previous study, a 32-nucleotide deletion of the chemokine receptor-5Δ32 (CCR-5Δ32) was strongly associated with the incidence of ITBL in adult liver transplantation. This study re-evaluates the association of CCR-5Δ32 gene polymorphism and the incidence of ITBL. 169 patients were included into this retrospective
analysis. 134 patients were homozygous for wild-type CCR-5, 33 patients heterozygous, and 2 patients were homozygous for CCR-5Δ32 mutation. There were no major differences in donor or recipients demographics. No association was found between CCR-5Δ32 mutation and the development of ITBL. We conclude that CCR-5Δ32 is no risk factor for the development of ITBL in our patient cohort.


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## Body

## 1. Introduction

The terms “nonanastomotic biliary strictures”, “intrahepatic biliary strictures”, or “ischemic-type biliary lesion” (ITBL) are
often used as synonyms for hilar or intrahepatic diffuse bile duct strictures,
necrosis, ecstasies, or dilatations (see Figure1) [1, 2]. The reported
incidence of ITBL after OLT varies between 1.4% and 20% [3–5]. Some centers report even higher incidence [6]. Patient and graft survival after the
diagnosis of ITBL are significantly reduced [7]. ITBL is the third most common reason for hepatic retransplantation [8].
This complication encounters for major morbidity and mortality, creates high
costs, and aggravates organ shortage [7, 8].Figure 1
Intrahepatic presentation of ischemic-type biliary lesion six months after hepatic transplantation for chronic hepatitis B-associated liver cirrhosis. The patient's hepatic artery is patent, and there is no other known cause for the destruction of the intrahepatic biliary tract.The exact cause of ITBL still remains unclear. Only relevant risk
factors are described. However, data about risk factors for the development of
ITBL are inconsistent. A recent study on 1113 liver transplant patients showed
no relevant donor or recipient risk factor of ITBL [5]. There are only
two studies evaluating the impact of chemokine receptors (CCR) on the
development of ITBL [6, 9]. In Moench's study on 146 OLT patients CCR-5Δ32 mutation was evaluated and correlated
with a significant increased incidence of ITBL [6]. A recent study on
137 pediatric liver transplants failed to show an association between CCR-5Δ32 and biliary complications [9].
CCR-5Δ32 is a single base-pair deletion of CCR-5 that
leads to a nonfunctional receptor [10]. The clinical impact of this
mutation was first described for homozygous CCR-5Δ32 Caucasians being highly resistant to HIV-1
infection [11]. If there was an immunological cause for ITBL, a
nonfunctional CCR might be relevant for this complication. Homozygous CCR-5Δ32 patients showed a significant increased
renal allograft survival [12]. Experimental studies correlated a
nonfunctional CCR-5 with less acute rejection episodes in lung [13], heart [14] and islet cell transplantation [15].The aim of this study was to re-examine a
correlation of CCR-5Δ32 genotype with the susceptibility of ITBL
within our patients.


## 2. Patients
and Methods

169 liver transplant patients were analyzed
retrospectively. All patients were transplanted at the transplant center of the
Humboldt University of Berlin between 03/2002 and 03/2005 and were included
during routine Follow-up examination. Follow-up period was 24 months minimum.
11 patients with the established diagnosis of ITBL, that were transplanted
earlier than 03/2001, were selectively included into this study due to the low
incidence of ITBL of only 4.0% within our patients. The diagnosis of ITBL was
made within the first year after transplantation in 82% of the patients. The
following demographic data were extracted from the hospital records and
evaluated: age, gender, underlying liver disease, blood group, Child-Pugh score
(CPS), model for end stage liver disease score (MELD score), initial
immunosuppression, cytomegalovirus infection (CMV), HLA match, donor age and
gender, donor serum sodium, cause of brain death and length of stay on
intensive care unit (ICU) prior to organ harvesting. 154 patients received a
cadaver graft, 15 patients received a graft from a living donor. Altogether, 19
split-liver transplantation were included. The local ethic committee approved the
study. Written informed consent was obtained from all patients before blood was
taken for DNA analysis.


## 3. Definition
of ITBL

ITBL was defined as nonanastomotic intra- or
extrahepatic biliary strictures without any history of hepatic artery
complications, ABO, incompatibility or other known causes of bile duct damages.
In all cases patency of the hepatic artery was proved by Doppler ultrasound,
computer tomography based angiography or conventional angiography. Recurrence
of primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) and
vanishing bile duct syndrome were ruled out in all cases by liver biopsy.
Diagnosis of ITBL was always established with endoscopic retrograde
cholangiography or percutaneous transhepatic cholangiography.


## 4. Genotype Analysis

All
genotype analyses were performed at the Johannes Gutenberg University of Mainz,
Department of Transplantation Surgery. For analysis of the CCR-5 genotype,
genomic DNA was prepared from 200μL peripheral blood using the QIAamp DNA blood
kit (Qiagen, Cologne, Germany). 2.5 μL of DNA were amplified by PCR using the
following CCR-5 specific primers: CCR-sense, 5′-CAAAAAGAAGGTCTTCATTACACC-3′
and CCR-5-antisense, 5′-CCTGTGCCTCTTCTTCTCATTTCG-3′. The PCR mixture was
composed of 2.5 μL 10 x PCR buffer (Roche Molecular Systems,
Mannheim, Germany), 0.5 μL of 12.5 mmol/L dNTP (PeqLab, Erlangen,
Germany,), 2.5 μL of each sense and antisense primer (10 μmol/L), and 1.25 U AmpliTag DNA polymerase
(Roche Molecular Systems) in a total volume of 25 μL. Forty PCR cycles were run on a Genius
thermocycler (Techne, Cambridge, UK), using the following temperature profile:
initial denaturation, 94°C 3 minutes; amplification, 94°C 1 minute, 64°C 1
minute, and, 72°C 1 minute (40 cycles); terminal elongation, 72°C 9 minutes. The size
of the wild-type product was 189 base pairs (bp), and the CCR-5Δ32 allele yielded a product of 157 bp. PCR
products were analyzed by 2% agarose gel electrophoresis.


## 5. Statistical
Analysis

All statistical calculations were performed in
SPSS 11.3 (SPSS Inc., Chicago, USA). Data are given as mean values ± standard deviation. Descriptive statistics
were used to summarize the donor and recipients characteristics. For
independent variables, cross tabulations and chi-square tests were performed.
Nonparametric variables were evaluated with Fisher’s exact test,  and asymptotic
significance was calculated.All of the tests performed were two-sided.P-values of   P < .05 were considered as statistically significant. All
calculations were performed in association with the Department of Biometrical
Medicine of the Humboldt University of Berlin.


## 6. Results

### 6.1. Patient Characteristics and Genotype Distribution

A total
number of 169 liver transplant recipients were available for genotyping and
complete data analysis. Gender and age were equally distributed between
wild-type group (wt/wt) and heterozygous CCR-5Δ32 group (wt/Δ32). Patients in the homozygous group (Δ32/Δ32) were female and male. The observed genotype
frequency was as expected assessed by Hardy-Weinberg equilibrium in the study
population. There were no differences between wt/wt group and wt/Δ32 group regarding to CPS score, MELD score or
blood group (Table 1).Table 1
Recipient characteristics. MELD: model for end-stage liver disease; CPS: Child-Pugh score; BG: recipients blood group; wt/wt: wild-type CCR-5; wt/Δ32: heterozygous CCR-5Δ32; Δ32/Δ32: homozygous CCR-5Δ32; CMV: cytomegalovirus; OKT-3: monoclonal
murine anti-CD-3 antibody.
Recipient
characteristicsVariableswt/wtwt/Δ32Δ32/Δ32P-valuen (169)134
(79.3%)33
(19.5%)2
(1.2%)Recipient genderMale89
(66.4%)22
(66.7%)—.137Female45
(33.6%)11
(33.3%)2
(100%)Mean recipient age (years)50.2±10.349.8±9.947.5±17.7.443MELD Score (mean ± SD)17.2±8.717.9
±  9—.960CPS A13
(11.8%)4
(16%)1
(50%).487CPS B60
(54.5%)13
(52%)1
(50%)CPS C37
(33.7%)8
(32%)—BG A52
(39.1%)10
(30.3%)1
(50%).823BG B19
(14.3%)4
(12.1%)—BG AB15
(11.3%)3
(9.1%)—BG O47
(35.3%)16
(48.5%)1
(50%)Hepatitis B-related cirrhosis16
(11.9%)3
(9.1%)—.918Hepatitis C-related cirrhosis21
(15.7%)6
(18.2%)—Hepatocellular carcinoma19
(14.2%)4
(12.1%)—Primary biliary cirrhosis6
(4.5%)—2
(100%)Primary sclerosing cholangitis4
(3%)2
(6.1%)—Acute liver failure4
(3%)3
(9.1%)—Autoimmune hepatitis2
(1.5%)——Metabolic liver diseases2
(1.5%)3
(9.1%)—Alcohol-induced cirrhosis41
(30.6%)9
(27.3%)—Retransplantation4
(3%)1
(3%)—Others15
(11.2%)2
(6.1%)—Cold ischemic time (minutes)533
±
144582
±
202633.806Initial ImmunosuppressionTacrolimus110
(82.6%)28
(84.8%)2
(100%).824Cyclosporine A23
(17.2%)4
(12.1%)—others1
(0.7%)1
(3.0%)—HLA match0 match24
(26.4%)6
(27.3%)2
(100%).4481 match40
(44.0%)8
(36.4%)—2 matches21
(23.1%)5
(19.2%)—3 matches5
(5.5%)2
(9.1%)—4–6 matches1
(1.1%)1
(4.5%)—CMV Infectionpostitve43
(32.1%)12
(36.4%)2
(100%).117negative28
(20.9%)2
(6.1%)—unknown63
(47.0%)19
(57.6%)—There were
no statistical significant differences in the composition of underlying liver
disease of group wt/wt and wt/Δ32. Both patients with Δ32/Δ32 had primary biliary cirrhosis as underlying
liver disease.Initial
immunosuppression was tacrolimus based in 82.6% in the wt/wt group compared to
84.8% in the wt/Δ32 group. Likewise, cold ischemic time and HLA
match showed no differences between groups. Both homozygous Δ32 patients had zero HLA match. CMV infection
that demanded ganciclovir treatment was present in approximately 30% in the
wt/wt and wt/Δ32 group and in both homozygous patients.


### 6.2. Donor Characteristics

There were
no differences between group regarding donor age or gender. Donors of groupΔ32/Δ32 were younger (35.7 years versus 46.5 years and
48.5 years). Mean donor serum sodium was 146.9 mmol/L in the wt/wt group
compared with 147.7 mmol/L in the wt/Δ32 group and 155.5 mmol/L in the Δ32/Δ32 group. Data of causes of brain death and
length of stay on the ICU prior to organ harvesting are shown in Table 2.Table 2
Donor characteristics. ICU: intensive care unit; wt/wt:
wild-type CCR-5; wt/Δ32: heterozygous CCR-5Δ32; Δ32/Δ32: homozygous CCR-5Δ32.
Donor
characteristicswtwt/Δ32Δ32/Δ32P-valueDonor age (years)46.5±17.248.5±16.535.7±11.2.663Donor genderMale76 (56.7%)20 (60.6%)1 (50%).901Female58 (43.3%)13 (39.4%)1 (50%)Mean donor serum Na+ (mmol/L)146.9±8.4147.7±7.9155,5 ± 27.5.552Cause of brain deathSubarachnoidal
bleeding75 (56%)16 (48.5%)1 (50%).866Trauma31 (23.1%)8 (24.2%)—Intracerebral bleeding1 (0.7%)1 (0.6%)—Hypoxia3 (2.2%)——Brain tumor1 (0.7%)——Cardiac infarction1 (0.7%)——Cerebral infarction10 (7.5%)3 (9.1%)—others12 (9%)5 (15.2%)1 (50%)Stay on the ICU prior to Organ harvesting (days)4.3±4.74.7±3.87.0.564


### 6.3. Incidence ITBL and Rate of Retransplantation

Incidence
of ITBL was 11.2% in this study due to the selection of patients with ITBL that
were additionally included into this evaluation. HomozygousΔ32 patients developed no ITBL compared to 11.2%
and 12.1% of homozygous wild-type patients and heterozygous patients,
respectively. The rate of retransplantation was 3.0% in both wt/wt and wt/Δ32 group (see Table 3). Retransplantation of
the heterozygous patient was indicated due to chronic ductopenic rejection
following OLT for PSC. In the wt/wt group, the indications for retransplantation
were INF, cryptogenic recirrhosis, and ITBL.Table 3
Events after transplantation. wt/wt: wild type CCR-5; wt/Δ32: heterozygous CCR-5Δ32; Δ32/Δ32: homozygous CCR-5Δ32; ITBL: ischemic-type biliary lesion; Re-OLT:
retransplantation.
Incidence of ITBL or Re-transplantationEventswt/wtwt/Δ32Δ32/Δ32P-valuen134332No ITBL119
(88.8%)29
(87.9%)2(100%).870ITBL15
(11.2%)4
(12.1%)No Re-OLTx130
(97%)32
(97%)2
(100%).970Re-OLTx3(3%)1
(3%)—


## 6.1. Patient Characteristics and Genotype Distribution

A total
number of 169 liver transplant recipients were available for genotyping and
complete data analysis. Gender and age were equally distributed between
wild-type group (wt/wt) and heterozygous CCR-5Δ32 group (wt/Δ32). Patients in the homozygous group (Δ32/Δ32) were female and male. The observed genotype
frequency was as expected assessed by Hardy-Weinberg equilibrium in the study
population. There were no differences between wt/wt group and wt/Δ32 group regarding to CPS score, MELD score or
blood group (Table 1).Table 1
Recipient characteristics. MELD: model for end-stage liver disease; CPS: Child-Pugh score; BG: recipients blood group; wt/wt: wild-type CCR-5; wt/Δ32: heterozygous CCR-5Δ32; Δ32/Δ32: homozygous CCR-5Δ32; CMV: cytomegalovirus; OKT-3: monoclonal
murine anti-CD-3 antibody.
Recipient
characteristicsVariableswt/wtwt/Δ32Δ32/Δ32P-valuen (169)134
(79.3%)33
(19.5%)2
(1.2%)Recipient genderMale89
(66.4%)22
(66.7%)—.137Female45
(33.6%)11
(33.3%)2
(100%)Mean recipient age (years)50.2±10.349.8±9.947.5±17.7.443MELD Score (mean ± SD)17.2±8.717.9
±  9—.960CPS A13
(11.8%)4
(16%)1
(50%).487CPS B60
(54.5%)13
(52%)1
(50%)CPS C37
(33.7%)8
(32%)—BG A52
(39.1%)10
(30.3%)1
(50%).823BG B19
(14.3%)4
(12.1%)—BG AB15
(11.3%)3
(9.1%)—BG O47
(35.3%)16
(48.5%)1
(50%)Hepatitis B-related cirrhosis16
(11.9%)3
(9.1%)—.918Hepatitis C-related cirrhosis21
(15.7%)6
(18.2%)—Hepatocellular carcinoma19
(14.2%)4
(12.1%)—Primary biliary cirrhosis6
(4.5%)—2
(100%)Primary sclerosing cholangitis4
(3%)2
(6.1%)—Acute liver failure4
(3%)3
(9.1%)—Autoimmune hepatitis2
(1.5%)——Metabolic liver diseases2
(1.5%)3
(9.1%)—Alcohol-induced cirrhosis41
(30.6%)9
(27.3%)—Retransplantation4
(3%)1
(3%)—Others15
(11.2%)2
(6.1%)—Cold ischemic time (minutes)533
±
144582
±
202633.806Initial ImmunosuppressionTacrolimus110
(82.6%)28
(84.8%)2
(100%).824Cyclosporine A23
(17.2%)4
(12.1%)—others1
(0.7%)1
(3.0%)—HLA match0 match24
(26.4%)6
(27.3%)2
(100%).4481 match40
(44.0%)8
(36.4%)—2 matches21
(23.1%)5
(19.2%)—3 matches5
(5.5%)2
(9.1%)—4–6 matches1
(1.1%)1
(4.5%)—CMV Infectionpostitve43
(32.1%)12
(36.4%)2
(100%).117negative28
(20.9%)2
(6.1%)—unknown63
(47.0%)19
(57.6%)—There were
no statistical significant differences in the composition of underlying liver
disease of group wt/wt and wt/Δ32. Both patients with Δ32/Δ32 had primary biliary cirrhosis as underlying
liver disease.Initial
immunosuppression was tacrolimus based in 82.6% in the wt/wt group compared to
84.8% in the wt/Δ32 group. Likewise, cold ischemic time and HLA
match showed no differences between groups. Both homozygous Δ32 patients had zero HLA match. CMV infection
that demanded ganciclovir treatment was present in approximately 30% in the
wt/wt and wt/Δ32 group and in both homozygous patients.


## 6.2. Donor Characteristics

There were
no differences between group regarding donor age or gender. Donors of groupΔ32/Δ32 were younger (35.7 years versus 46.5 years and
48.5 years). Mean donor serum sodium was 146.9 mmol/L in the wt/wt group
compared with 147.7 mmol/L in the wt/Δ32 group and 155.5 mmol/L in the Δ32/Δ32 group. Data of causes of brain death and
length of stay on the ICU prior to organ harvesting are shown in Table 2.Table 2
Donor characteristics. ICU: intensive care unit; wt/wt:
wild-type CCR-5; wt/Δ32: heterozygous CCR-5Δ32; Δ32/Δ32: homozygous CCR-5Δ32.
Donor
characteristicswtwt/Δ32Δ32/Δ32P-valueDonor age (years)46.5±17.248.5±16.535.7±11.2.663Donor genderMale76 (56.7%)20 (60.6%)1 (50%).901Female58 (43.3%)13 (39.4%)1 (50%)Mean donor serum Na+ (mmol/L)146.9±8.4147.7±7.9155,5 ± 27.5.552Cause of brain deathSubarachnoidal
bleeding75 (56%)16 (48.5%)1 (50%).866Trauma31 (23.1%)8 (24.2%)—Intracerebral bleeding1 (0.7%)1 (0.6%)—Hypoxia3 (2.2%)——Brain tumor1 (0.7%)——Cardiac infarction1 (0.7%)——Cerebral infarction10 (7.5%)3 (9.1%)—others12 (9%)5 (15.2%)1 (50%)Stay on the ICU prior to Organ harvesting (days)4.3±4.74.7±3.87.0.564


## 6.3. Incidence ITBL and Rate of Retransplantation

Incidence
of ITBL was 11.2% in this study due to the selection of patients with ITBL that
were additionally included into this evaluation. HomozygousΔ32 patients developed no ITBL compared to 11.2%
and 12.1% of homozygous wild-type patients and heterozygous patients,
respectively. The rate of retransplantation was 3.0% in both wt/wt and wt/Δ32 group (see Table 3). Retransplantation of
the heterozygous patient was indicated due to chronic ductopenic rejection
following OLT for PSC. In the wt/wt group, the indications for retransplantation
were INF, cryptogenic recirrhosis, and ITBL.Table 3
Events after transplantation. wt/wt: wild type CCR-5; wt/Δ32: heterozygous CCR-5Δ32; Δ32/Δ32: homozygous CCR-5Δ32; ITBL: ischemic-type biliary lesion; Re-OLT:
retransplantation.
Incidence of ITBL or Re-transplantationEventswt/wtwt/Δ32Δ32/Δ32P-valuen134332No ITBL119
(88.8%)29
(87.9%)2(100%).870ITBL15
(11.2%)4
(12.1%)No Re-OLTx130
(97%)32
(97%)2
(100%).970Re-OLTx3(3%)1
(3%)—


## 7. Discussion

The
problem of genetic association studies and complex clinical syndromes or
diseases must be addressed. One can always question the usefulness of these
studies that   are often   even small in sample size. Most of these studies are
statistically underpowered. On the other side, it seems important to undertake
replication studies for reported associations between genetic polymorphisms and
diseases, especially in diseases of major clinical importance.In this
study, the distribution of heterozygousΔ32 and homozygous Δ32 mutation was very consistent with  the
published data of the global distribution of this gene polymorphism [10, 16]. Heterozygous and homozygous genotypes occur
in Caucasian population in 15%–20% and 1%, respectively [16]. Heterozygous individuals show no abnormal
receptor function compared with wt/wt individuals. All examined donor and
recipient factors showed no statistical differences between groups. This seems
important due to the small number of patients included in this study and the
possible bias by including selected patients with the diagnosis of ITBL into
the study cohort.Despite
increasing success rates in clinical OLT over the past decades, ITBL remains a
major cause for recipient morbidity and mortality [1–5]. This single
complication creates enormous costs and aggravates organ shortage. Up till
today, only risk factors for ITBL could be identified in various clinical
studies. The length of cold ischemic time was correlated with the development
of ITBL [1–4]. Donor age was found to be a significant risk factor for
ITBL. Other studies were not able to show these correlations [5].
Immunological causes seem to play only a minor role in the pathogenesis of
ITBL. Moench et al. described a single base-pair deletion in the coding region
of the chemokine receptor-5Δ32, CCR-5Δ32, to be a significant risk factor for the
development of ITBL. In Moench's study on 146 OLT patients CCR-5Δ32 was a significant risk factor for ITBL
(incidence of ITBL in CCR-5Δ32 patients was 30% versus 11.7% in CCR-5
wild-type patients) and was correlated with a decreased survival rate after
OLT. The overall ITBL rate was 15% [6]. The different incidence of ITBL of the study by
Moench and this study may be a reason for the different findings, even though
both investigators used the same definition of ITBL. Donors were younger in
this study with 38.2 ± 16
(non-ITBL patients) and 42.9 ± 17 (ITBL)
versus 46 ± 14
(non-ITBL) and 52 ± 14 (ITBL)
in Moench's study. However, cold ischemic time was shorter in Moench's
investigation (564 minutes  (ITBL) and 538  minutes (non-ITBL) versus 637  minutes (ITBL) and
558  minutes (non-ITBL)). The use of arterial back table perfusion was also
routinely done for all organs that were harvested by a team of our own.
Fischer-Maas et al. analyzed CCR-5Δ32 polymorphism in 137 pediatric patients but
showed no correlation with biliary complications [9]. The incidence of
ITBL varies between 1.4% and 20% according to the literature, which might be a
problem of different definition of this disease [3–5]. The rate of ITBL in our OLT
patients (2100 patients between 1988 and 2004) is 4.0%. In the presented study
on 169 OLT patients the overall incidence of ITBL was 11.7%, but only due to a
selective inclusion of patients with the established diagnosis of ITBL. This
practice of patient recruitment may be criticized, but we think it is justified
according to our low incidence of ITBL. Thus, it was possible to investigate 19
patients with ITBL. ITBL rate in CCR-5Δ32 patients was virtually equal to the one in
CCR-5 wild-type patients. No statistically significant differences regarding
ITBL or retransplantation were observed.Why would
CCR-5Δ32 mutation promote the development of ITBL? CCR-5Δ32 is a 32-base-pair deletion within the
coding region of CCR-5, which results in a frame shift and generates a
nonfunctional receptor [11].
Homozygous expression of CCR-5Δ32 is associated with a reduced risk of
asthma and with a reduced severity of rheumatoid arthritis [17, 18],
multiple sclerosis [19, 20], and primary biliary cirrhosis (PBC) [21]. In other words, the nonfunctional nature of
CCR-5Δ32 protects the individual from autoimmune
diseases where CCR-5 seems to play a central pathophysiological role. These
data do not backup the theory, that immunological risk factors are dominant in
the development of ITBL. Likewise, a correlation of a reduced survival rate
with CCR-5Δ32 would not be consistent to the literature,
where CCR-5Δ32 mutation is associated with an increased
survival in renal [12], lung [13], heart [14] and islet
cell transplantation [15]. In contrast
to those findings, CCR-5Δ32 is strongly associated with an increased
severity of PSC [22]. Patients suffering from PSC have been
described as carrying a higher risk for ITBL, with a reported significantly
increased incidence of 15.8% to 25% [1, 8, 23]. Another study reported PSC as the only
independent risk factor for ITBL with an incidence of 31% compared with 9%  of the
control group [24]. However,
the problem of differentiation between ITBL and recurrence of PSC must be addressed.
Recurrence rates of 8.6% to 25% were described for PSC after OLT [25–27]. The diagnose of recurrence
of PSC is based on cholangiographic findings of intrahepatic, hilar and/or
exrahepatic strictures, duct irregularities and on the histopathological picture
of fibrous cholangitis and/or fibro-obliterative lesions with or without
ductopenia, biliary fibrosis, or biliary cirrhosis [28]. Most of these findings are neither
pathognomonic for either recurrence of PSC nor ITBL [29]. All patients with ITBL in this study
underwent percutaneous liver biopsy, and our pathologists ruled out PSC
recurrence. There remains a diagnostic uncertainty.Since two
of three studies failed to show an association between ITBL and CCR-5Δ32 gene polymorphism, a general recommendation
for screening of OLT patients for CCR-5Δ32 does not seem to be justified.



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*Source: 436515-2009-03-30.xml*