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Clostridium Difficile Infection and Liver Disease
Saif Musa, Carl Moran, Tony Rahman
Department of Gastroenterology & Hepatology, St. George’s Hospital, Blackshaw Rd, London, UK
Abstract
The rates of the predominantly hospital acquired
infection, Clostridium difficile, have increased throughout
the world. Several risk factors and susceptible patient
populations have been identified. Patients with pre-existing
liver disease represent an important cohort; recent evidence
suggests that Clostridium difficile infection (CDI) is
associated with a worse outcome and increased health care
costs. This review focuses on the epidemiology, risk factors,
pathogenesis, treatment options and outcomes associated
with CDI in patients with liver disease.
Keywords
Clostridium difficile – Clostridium difficile infection
enterocolitis – pseudomembranous – epidemiology – liver
diseases – risk factors and treatment.
Introduction
Reports of liver disease (LD) patients infected by the
bacterium Clostridium difficile (C. difficile) first emerged
more than 25 years ago [1-5]. Since then, Clostridium
difficile infection (CDI) has been described in a variety
of LD patients including those with acute and chronic
(cirrhotic) conditions and those post liver transplantation
(LT) [1-15]. Important risk factors have been identified and
recent evidence suggests infected LD patients have increased
morbidity, mortality and health care costs [6, 16,17]. This
narrative review focuses on the epidemiology, risk factors,
treatment options and outcomes in LD patients with CDI.
Received: 21.07.2010Accepted: 28.08.2010
J Gastrointestin Liver Dis
September 2010 Vol.19 No 3, 303-310
Address for correspondence:
Dr. Tony M. Rahman
Department of Gastroenterology and Hepatology, St. George’s Hospital
Blackshaw Road, London
SW17 0QT, UK
Email: [email protected]
Epidemiology of Clostridium difficile
infection and LD
Clostridium difficile infection can either be classified
as hospital or community acquired; the prevalence of
LD has been described in both. In terms of nosocomial
disease, retrospective single centre studies have revealed
CDI is common amongst LT patients [8], and patients of
a hepatology unit [13]. The former revealed 30/136 (22%)
hospital acquired cases occurred in LT patients and the latter
showed that compared to other hospital wards, higher rates
of infection were evident on the hepatology ward (0.9% vs
0.29%). Most of the affected patients (22/23) in the latter case
controlled study had cirrhotic LD [Child Pugh A (17%), B
(50%) or C (28%)]. Two large multicentre studies have also
described the frequency of LD amongst hospitalised patients.
The first, the Canadian Nosocomial Infection Surveillance
Program (CNISP) reported 62/1430 (4%) CDI cases had
underlying LD [16], and the second, a retrospective study
from the United States (US) revealed 1,165/59,385 (2%)
CDI cases discharged from hospital either had cirrhosis or
cirrhosis related complications [6]. Both of these findings
require further clarification; the definition of LD used by the
CNISP was not mentioned and the reported rate in cirrhotics
may have included asymptomatic carriers.
The proportion of nosocomial cases with acute or
chronic (non-cirrhotic) LD has yet to be determined; cases
in acute LD have rarely been described [1, 4]. One single
centre US study has used the term ‘mild LD’ but failed to
describe this any further. This investigation reported that
13/382 (3%) hospital acquired cases had mild LD [18]. The
prevalence of LD amongst community acquired cases has
also been rarely described [19, 20]. One case controlled
study revealed 2/1233 (0.2%) community acquired cases
had cirrhosis [20].
A number of studies have described the rates of CDI in
certain LD [6-8, 10, 14, 18, 20, 21]. Investigations involving
hospitalised patients have revealed that 2% of mild LD
patients and 5.5% of cirrhotics are diagnosed with CDI
[18, 21]. One case controlled study has demonstrated that
2/19 (11%) cirrhotic patients develop community acquired
304
CDI [20]. Although diarrhoea on hospital admission has
been reported in 7/54 (13%) cirrhotic patients with CDI
[6], it is not clear whether all/any really fulfil the criteria
for community acquired CDI. The recurrence rate of CDI
varies from 15-35%; most are thought to be caused by
another strain [22]. Recurrent episodes of CDI have rarely
been described in patients with LD; rates post LT vary from
22-27% [8, 9].
Rates of CDI in patients with deceased donor LT vary
from 3% to 8% [8, 14] and post ‘live’ donor LT transplant
vary from 5% to 11% [9, 10]. Most cases (≥50%) occur within
the first month of LT [8, 9, 14]; reports in patients > 1 year
post LT are rare [8, 23]. The observed variance in rates may
be attributed to the method of diagnosis, the timing/number
of stool tests performed and study duration. Investigation
periods have varied from less than four years [8] to more than
eight [9]. A number of different techniques have been used to
identify cases including enzyme immunoassays (EIA), stool
cultures and polymerase chain reaction assays [7-9,11-13].
The specific method used may have influenced the diagnostic
rate. Enzyme immunoassays have been most frequently used
and whilst they are simple to perform and provide rapid
results, several types are available each exhibiting a range
of sensitivities and specificities compared to the reference
method (the cytotoxin stool cell culture assay) [24]. During
the first month post deceased donor LT, only 5/35 EIA
positive specimens were culture positive [7].
The spectrum of disease associated with CDI also
includes patients with asymptomatic disease. Currently little
is known about rates of asymptomatic carriage or hospital
acquisition in LD patients; most of the data available refers to
patients post LT [9, 25, 26]. Approximately 3% of the healthy
adult population are colonised by C.difficile, increasing to
over 20% in hospitalised patients [27]. Liver transplantation
has been shown to be an independent risk factor for hospital
acquisition (relative risk 4.2, 95% confidence interval [CI]
1.3-13.7) [25]. One small prospective study (n=15) revealed
nine (60%) patients were colonised during the first 35 days
post transplant [26]. Two thirds of cases were colonised by
toxin producing strains; none were stool culture or toxin
positive at the time of study induction. A more recent study
involving less frequent stool testing, determined 16/27 (60%)
LT patients with C.difficile were asymptomatic [9]. Only one
patient was however carrying a toxin producing strain. As
stool results on study entry were not reported, it is not possible
to say whether the asymptomatic carriers were present from
the time of admission or were cases of hospital colonisation
or a combination of both. Asymptomatic carriage amongst
cirrhotic patients may be as high as 20% [28].
Risk factors for Clostridium difficile
infection in patients with liver disease
Few studies have described the risk factors associated
with CDI in LD patients (Table I); those identified relate
to cirrhotic and LT patients [6, 8, 9, 13]. Although formal
comparisons between the rates and risk factors for CDI in
Musa et al
Table I. Risk factors associated with Clostridium difficile infection in
patients with liver disease
Hepatology inpatients [13]:
Autoimmune hepatitis diagnosis
Previous antibiotic use (Beta-lactams, Co-amoxiclav)
Cirrhotic inpatients[6]:
Inpatient antibiotic use
Outpatient proton pump inhibitor use
Post live donor liver transplant [9]:
Male sex
Pre-operative serum creatinine ≥1.5mg/dL
Post deceased donor liver transplant [8] :
Primary non-function liver disease diagnosis
United Network Organ Status
Non-primary liver transplantation
Elevated model end stage liver disease score
Renal impairment in donor
Post-operative intra-abdominal bleed
Post-operative biliary complications
Post-operative bacterial/systemic infection
Post-operative wound complications
Post-operative residency on intensive care
patients receiving a deceased donor LT or live donor LT have
yet to be done, different risk factors have been reported.
Independent risk factors during the first three months of ‘live’
donor LT include male gender (odds ratio - OR 4.56, 95% CI
1.02-33.3) and an elevated pre-operative serum creatinine
≥1.5mg/dl (OR 15.99, 95% CI 3.85-68.3) [9]. Impaired
host immunity in patients with deranged renal function may
explain the latter finding. In contrast, a number of other
risk factors have been identified in patients post deceased
donor LT (Table I); stratification by CDI onset (early or
intermediate) has revealed some important differences [8].
Early CDI (<28 days of LT) is associated with a
higher model end stage liver disease (MELD) score, intraabdominal haemorrhage, increased numbers of grafts and
re-transplantation. In contrast, intermediate CDI (29-365
days post LT), is more likely in patients with vascular
complications, bacterial infections and those requiring
endoscopic retrograde cholangiopancreatography or
percutaneous cholangiography [8]. Biliary complications,
bile leaks and systemic infections are common to both.
As the relationship in terms of antibiotic exposure was not
assessed, there is the possibility that antibiotics used to treat
complications were more important than the underlying
cause. Biliary complications are also common after ‘live’
donor LT, however, the relationship to CDI has not been
reported [29].
Antecedent antibiotic therapy is the most important
risk factor for CDI, and antibiotic use in patients with
cirrhosis and post LT is significant. Patients requiring LT
routinely receive antibiotics as part of their management
and whilst pre-operative antibiotic use [9], and selective
decontamination have not been shown to increase the risk
of CDI [30], the use of additional post-operative antibiotics
maybe important [8]. This study demonstrated that 69%
CDI patients post LT received additional antibiotics. One
C. difficile and liver disease
prospective, double blinded, randomised control trial has
evaluated the risk of CDI in LT patients receiving selective
bowel decontamination [30]. No significant difference
in rates was observed between patients (n=37) receiving
80 mg gentamicin, 100mg polymyxin E and 2 million units of
nystatin and patients (n=43) receiving 2 million units nystatin
alone (5.4% vs 2.3%, p=0.905). In terms of post-operative
antibiotics, the class/type may be of more importance
than the number [9]. This study failed to demonstrate any
association between CDI and the number of post-operative
antibiotics (<6 vs ≥6).
In terms of cirrhotic patients, one recent retrospective
case controlled study has identified in-patient antibiotic
use as an independent predictor of CDI (OR 11.6, 95% CI
2.63-51.05) [6]. The type of antibiotic administered may
have influenced this result. Third generation cephalosporins
(48% vs 20%) and beta lactams (19% vs 7%) were more
commonly prescribed amongst affected individuals; both are
considered as high risk antibiotics for CDI [31]. Interestingly,
outpatient antibiotic use (ciprofloxacin) was not shown to
be a significant risk factor [6, 17]. Fluoroquinolone use has
been linked to recent outbreaks and the emergence of a
hypervirulent C. difficile strain in North America [32, 33].
The risk of CDI in LD patients requiring the rifamycin
class of antibiotic requires further clarification; evidence
suggests that rifaximin reduces the risk of hepatic
encephalopathy and may prove an important treatment option
[34, 35, 36]. In contrast to the suggested relationship with
rifampicin [1, 3], rifaximin does not significantly increase
the risk of infection [33, 34] and may be an effective
therapy in recurrent cases [37]. Rifaximin administration in
conjunction with lactulose (n=140) has not been shown to
significantly increase the risk of CDI, compared to patients
(n=159) receiving lactulose alone (1.4% vs 0%) [34]. This
result needs to be interpreted with caution; lactulose may
have played an important ‘protective’ role by reducing
short chain fatty acid production and suppressing C.difficile
growth/proliferation [28].
Immunosuppressant medications are an important
risk factor for CDI in other patient populations including
recipients of renal transplants and patients with inflammatory
bowel disease [38-40]. Immunosuppressant medication
is often required in certain LD, especially auto-immune
hepatitis and post LT. Autoimmune hepatitis is associated
with an increased risk of nosocomial CDI (26% cases vs
2% controls, p<0.01) [13]. The criteria used by this study to
define autoimmune hepatitis included evidence of interface
hepatitis, absence of other causes of liver disease, and the
presence of autoantibody titer > 1:40. Patients post LT
require immunomodulators such as tacrolimus, steroids and
mycophenolate to reduce the risk of rejection. Although
‘acute rejection’ per se does not appear to increase the risk of
CDI [8, 9], specific ‘acute rejection’ treatments may. Patients
requiring whole plasma exchange have demonstrated a
trend towards increased rates of infection [8]. Several
immunosuppressants are currently being used/developed
for patients with LT and whether certain drugs are more
305
frequently associated with CDI has yet to be evaluated [41].
Corticosteroid use has been identified as a significant risk
factor for relapses in transplant patients (risk ratio 4.19, 95%
CI 1.41-13.06) [11]. Another common risk factor associated
with CDI - age - has not been not shown to be important in
cirrhotic or post LT patients [6, 9, 13].
The relationship between proton pump inhibitor (PPI) use
and CDI remains unclear; studies involving both community
and hospital acquired cases have produced conflicting results
[20, 32, 42, 43]. Reduced gastric acid is believed to play an
important role in ensuring survival of any ingested active
(vegetative) forms of C. difficile [44]. In addition PPIs may
also suppress the immune response to infection [45]. The
only study to evaluate the relationship between PPI use
and CDI in LD patients has involved cirrhotic patients.
This investigation revealed that outpatient PPI use was an
independent risk factor for CDI (OR 37.6, 95% CI 6.22227.6) [6]. This finding suggests that a judicious prescribing
policy may be required in this cohort [17]: one prospective
study has shown that 39/51 (63%) of cirrhotics receive PPIs
inappropriately [46].
Other possible risk factors in cirrhotics have also been
described [6]. Although the tertiary referral component (58
infected vs 108 non-infected cirrhotics) of this study failed
to show any association with age, gender or ethnicity, the
nationwide component (n=1,165 infected vs 82,065 noninfected cirrhotics) demonstrated that infected cirrhotics
were more likely (p<0.001) to be older (61 vs 58 years),
female (46.0% vs 38.5%), Caucasian (57.4% vs 51.4%)
and have a raised Charlson co-morbid score ≥ 3 (14.0 % vs
11.9%). In addition, CDI was found to be more common
(p<0.001) amongst cirrhotics with hepatorenal syndrome
(4.8% vs 3.0%), pneumonia (14.2% vs 7.8%), spontaneous
bacterial peritonitis (0.9% vs 0.5%) and a urinary tract
infection (21.3% vs 12.1%) and less common in cirrhotics
with encephalopathy (16.9% vs 19.0%) or a variceal bleed
(4.1% vs 7.9%).
Comparisons between patients with LD and CDI to
those with CDI alone have rarely been done [6]. This large
population based study demonstrated that infected cirrhotics
(n=1,165) were more likely (p<0.001) to be younger (61 vs
69 years), male (54.0% vs 40.8%) and Hispanic (11.6% vs
5.1%) than non-cirrhotic CDI patients (n=58,220) and less
likely to have a raised Charlson comorbid score ≥ 3 (14.0%
v18.8%), pneumonia (14.2% vs 17.2%) or a urinary tract
infection (21.3% vs 26.1%). Both cohorts excluded LT
patients.
Pathogenesis
Clostridium difficile is predominantly transmitted as
spores via the faecal-oral route. Following ingestion, primary
bile salts and their derivatives facilitate germination to the
vegetative (active) state within the small bowel. The bacteria
then migrates to the colon where under favourable conditions
(antibiotic mediated disruption of colonic flora), proliferation
occurs and strains capable of producing toxins (A,B) cause
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intestinal inflammation and disease [47, 48]. Disturbances
and thus reduced levels of colonic bacteria possessing the
enzyme 7-alpha hydroxylase activity, such as Lactobacillus
and Bifidobacteria species, are believed to play an important
role in facilitating C. difficile growth [47].
Altered gut flora has been reported in LD patients
[49-52], and may provide a favourable environment for
C.difficile colonisation and proliferation. All of these studies
have been conducted in Asia. Compared to normal controls,
cirrhotic patients (mostly with viral hepatitis) have been
shown to have significantly reduced levels of Bifobacterium
and increased levels of Clostridium, respectively [49]. In
addition to antibiotic use, possible reasons for the changes
in gut flora include delayed intestinal motility and increased
intestinal pH [49]. Reduced levels of Bifobacterium have
also been reported in patients with chronic severe hepatitis
and chronic hepatitis [51], and both Lactobacilli and
Bifidobacteria amongst alcoholic patients [52]. Experimental
animal models of acute liver failure have also demonstrated
reduced levels of Lactobacillus in the ileum and colon [52].
Selective bowel decontamination is predominantly aimed
at aerobic gram-negative bacteria. Maintenance of the gram
positive flora (including Bifidobacteria and Lactobacilli)
may provide a plausible explanation for the lack of any
association between selective bowel decontamination and
CDI in LT patients [30].
Not all patients colonised by toxin producing strains
develop disease; protective host factors include an intact
immune system and a lack of significant co-morbidity
[53,54]. Disturbed immune function has been observed in
patients with LD [13, 55] and may account for the apparent
increased risk in patients with autoimmune hepatitis [13].
Hypogammaglobulinaema may be an important risk factor in
LT patients; just over a quarter of LT patients have reduced
immunoglobulin levels (IgG levels <560 mg/dl) [55]. Risk
factors for reduced IgG levels include a diagnosis of non A/B
hepatitis, rare LD such as autoimmune hepatitis and reduced
platelet transfusion requirements. Although this study did not
assess outcome in terms of CDI, hypogammaglobulinaema
is associated with CDI in other patient populations e.g. those
post cardiac transplantation [55, 56].
Clinical features
The clinical manifestations associated with CDI are
diverse, ranging from asymptomatic carriage through to
severe colitis and life threatening sepsis [22]. Symptom onset
is variable and may range from one day to several weeks
following antimicrobial exposure [57]. Typical features of
CDI include watery diarrhoea and abdominal discomfort.
Systemic features develop in patients with more severe
disease and in some cases an ileus/megacolon may develop
[22]. Recent national and international guidelines now
incorporate a number of clinical, laboratory and radiological
parameters to define severity [58-60].
Clinical features associated with CDI in LD have
been mostly described in LT patients, diarrhoea, fever and
Musa et al
abdominal pain are common presenting symptoms in this
cohort [9, 12, 61]. Diarrhoea may last for up to 43 days
(range 5-43 days) [9]. Diarrhoea is extremely common in
the first few weeks post LT and it is important to rule out
other infectious (e.g. Cytomegalovirus) or non-infectious
(e.g. drugs) causes [62]. Severe cases of CDI have also
been reported in this cohort [8, 9, 14, 63, 64]. Although
hospitalised transplant patients are more likely to develop
symptomatic CDI [25], one retrospective study has failed
to show any significant difference in severity (death,
intensive care unit admission or colectomy within 30 days
of diagnosis) between transplant (n=80) and non-transplant
patients (n=86) [11]. Fever (67%) and diarrhoea (13%) are
also common amongst cirrhotic patients with CDI [6].
Extra-intestinal CDI has been reported in patients with
LD [65], including splenic and liver abscesses [5,15]. Liver
disease patients with ascites are susceptible to developing
bacterial peritonitis and there have been a few instances in
which C. difficile has been cultured from peritoneal fluid
[5, 65, 66].
Diagnosis
Several methods of diagnosis are available including
microbiology (stool culture/toxin testing), histology and
endoscopy. The reference method of diagnosis is the stool
cytotoxin culture assay (detects Toxin B). Use of this
technique has now largely been superseded by the more
rapid technique of EIA. Concerns over the sensitivity and
specificity of EIA have resulted in a growing consensus to
confirm all positive EIA cases with the reference method
[24]. Use of a ‘two’ or ‘three’ step approach to diagnosis is
believed to be more cost effective than using the reference
method alone [22]. Most studies involving LD patients
have used EIA to diagnose CDI [7-9, 11, 12], additional
testing of positive EIA cases has rarely been done [7, 9].
Stool toxin analysis by polymerase chain reaction has also
been done [13].
Stool sampling from patients with an ileus may not be
possible; in such cases endoscopy and radiological findings
may provide important clues. Histological and endoscopy
findings in patients with CDI vary from non specific colitis
to pseudomembranous colitis (severest form of disease) [57].
Pseudomembranous colitis has been described in LT patients
and unique histological findings have also been reported
[14]. Two patients had mucosal evidence of neutrophilic
capillaritis/venulitis. Clinicians should also be alert to the
possibility of CDI in cirrhotic patients with computerised
tomography evidence of right colon pneumatosis or diffuse
colonic pneumatosis/pancolonic thickening [67].
Treatment
Management of CDI can be either medical and/
or surgical. Current medical treatment involves oral
metronidazole for mild to moderate CDI cases and oral
vancomycin +/- intravenous metronidazole for severe/ life
threatening cases [58, 60, 68]. Important additional measures
C. difficile and liver disease
include barrier nursing, antibiotic rationing, avoidance of
antimotility agents and hand washing. Disease severity
of CDI is a continuum and progression may occur hence
regular/daily assessment is recommended [58, 60, 68].
Several other treatment options are available/being evaluated
[31, 69], including the antibiotics rifaximin, tigecycline,
fidaxomicin and nitazoxanide. In addition, immunotherapy
and faecal transplantation may also prove to be effective in
the future. Recurrent CDI can occur in up to 35% of cases
and treatment maybe difficult, often requiring longer courses
of vancomycin or metronidazole. Other possible treatment
options include cholestyramine, tolevamer, immunoglobulin
infusions and the infusion of colonic bacteria [22, 31, 69].
Treatment of asymptomatic carriers is ineffective and not
recommended [70]. Although development of a vaccine for
high risk patients may prove beneficial, its application may
be limited in immunosuppressed patients.
Patients that fail to respond to medical therapy may
require a colectomy; symptom resolution is expected within
a mean time of 3-6 days [22]. Colectomy rates vary from
0.17% [71] to 3.5% [72] and are associated with a high
mortality (11.1-66%) [73, 74]. The recommended surgical
treatments are a subtotal colectomy and ileostomy [75],
or a total colectomy and ileostomy [76]. Indications for
colectomy include the development of peritonitis and toxic
megacolon, leucocytosis (>20x109/L) and a raised lactate
(2.2-4.9 mmol/L) may also serve as important markers
[77].
In terms of LD, the majority of reports and studies
have used vancomycin to treat CDI [1, 3, 4, 6, 9, 15, 23,
78]. Metronidazole has also been successfully used [8].
Cholestyramine has rarely been required [1]. Cholestyramine
binds to bile acid and is widely used to treat pruritus in
patients with cholestatic LD; its mechanism of action against
C.difficile involves binding toxins. Colectomies have rarely
been required [6, 8, 64, 79]; mortality rates following a
colectomy are much higher in cirrhotic than non-cirrhotic
patients [80]. Recurrences have also been infrequently
reported [1, 9, 15, 75]; episodes have been successfully
treated with either repeat courses of vancomycin or
metronidazole. One recent case series has also demonstrated
that rifaximin may prove an effective treatment option for
recurrent CDI in patients post LT [37].
The use of probiotics containing specific strains of
Lactobacilli and Bifidiobacteria have been shown to reduce
the rates of bacterial infection in patients post LT and have
also been shown to improve liver function in patients
with alcoholic liver disease and non-alcoholic fatty liver
disease [52, 81, 82]. In addition, combination therapy with
rifaximin and probiotics may also reduce the risk of hepatic
encephalopathy [35]. Use of specific probiotic strains
may not be effective in all patients with LD; the effect in
patients with viral hepatitis has been less dramatic [83].
Modulation of the intestinal flora may also help to prevent/
reduce rates of CDI. Probiotics may act by augmenting the
antibody response against Toxin A, suppressing C. difficile
colonisation, adhesion and invasion and by directly inhibiting
307
the actions of Toxin A and B [69]. Lactulose may also have
a preventative role against CDI in LD patients, possibly by
reducing colonic exposure to toxins [28].
Outcome
Amongst CDI cases, patients with comorbid LD are at
an increased risk of a severe outcome including admission
to an intensive care unit, surgery (colectomy) and/or death
(OR 2.62, 95% CI 1.12-6.15) [16]. One retrospective study
investigating CDI cases on ICU (n=278) revealed that 18/278
(6.5%) of patients had underlying cirrhosis; 5/18 (28%)
of these cases died [84]. Amongst CDI cases requiring a
colectomy, the presence of LD is infrequently reported: 11%
may have cirrhosis [79], and 5% may have had a LT [64].
Only one study has investigated the morbidity, mortality and
associated healthcare costs in CDI patients with LD. This
large retrospective study, involving cirrhotic patients [6],
demonstrated that infected cirrhotics (n=1,165) were more
likely (p<0.001) to die (13.8% vs 9.6%), have prolonged
hospital stays (mean stay 14.4 vs 12.7 days) and higher
healthcare costs ($79,351 vs $ 57,708) than patients with
CDI alone (n=58,220).
In terms of cirrhotic patient population alone, those
with CDI (n=1,165) are more likely to die (OR 1.79, 95%
CI 1.51-2.12), require longer lengths of hospital stay (7.1
days, 95% CI 6.2-8.1 days) and incur higher healthcare
costs ($40,596, 95% CI $ 31,870-$49,321), than those not
infected (n= 82,065) (p<0.001). The mortality rate was
influenced by ethnic (African American>Caucasians>
Hispanics), insurance group (uninsured>private>Medicare)
and geographical differences (midwest America<north east
America) [OR 0.75, 95 % CI 0.64 –0.88, p<0.01) [6].
Mortality was not influenced by hospital status (teaching vs
non-teaching) or setting (urban vs rural). After adjusting for
all these factors, CDI remained an independent risk factor
for in-hospital death amongst cirrhotics (OR 1.55, 95% CI
1.29–1.85). This study also demonstrated the mortality risk
associated with CDI was similar to those from other cirrhotic
related complications such as hepatic encephalopathy (OR
1.94, 95% CI 1.83-2.06), variceal bleeding (OR 1.63, 95%
CI 1.49-1.78), spontaneous bacterial peritonitis (OR 1.98,
95% CI 1.45-2.70) and ascites (OR 1.30, 95% CI 1.22-1.38),
highlighting the importance of CDI in this patient population.
In terms of LT patients, cases with CDI rarely die or require
colectomy [8, 9, 14].
Conclusions
It is important to recognise that whilst the proportion
of CDI cases that have underlying LD is relatively small,
affected patients are at risk of increased morbidity and
mortality. The significance of CDI amongst cirrhotic patients
and those post LT is increasingly being reported. However,
little is known about the rates and significance in patients
with acute and chronic non-cirrhotic LD. A small number
of studies have identified risk factors associated with CDI
in certain LD (post LT and cirrhotic) patient populations.
308
These require further validation and assessment in other
LD groups. Metronidazole and vancomycin are the main
treatment options available. Use of probiotics, in certain liver
conditions, and lactulose may help reduce rates of infection.
Recurrent cases have rarely been reported and the apparent
increase in socio-economic costs merit further evaluation.
Conflicts of interest
None declared.
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