Ewan
H Forrest, BMedBiol MD
MRCP
SMJ 2004 49(3): 84-87
Correspondence to: Ewan.Forrest@gvic.scot.nhs.uk
Abstract
Background: Patients with
alcoholic liver disease (ALD) presenting with jaundice have advanced chronic ALD
and/ or acute alcoholic hepatitis. Their prognosis is poor. These patients may
be managed by General Medical physicians (GM) or by Gastroenterologists (GE).
Aim: This study aimed to
retrospectively assess the differences in management and outcome of jaundiced
ALD between GM and GE.
Patients and Methods:
Patients with a serum bilirubin
greater than 80 mmol/l
on admission and a history of alcohol excess until within three weeks of
admission were identified retrospectively. In particular the use of
corticosteroids (CS), nutritional support (N) and the use of broad-spectrum
antibiotics (A/b) were noted.
Results: 97 patients were
identified, 62 managed by GE. Differences were apparent between GE and GM
managed patients with respect to CS (p=0.017), N (p<0.001) and A/b
(p<0.001). The overall mortality was 27.8%, 34.0%, and 37.1% at 28, 56, and
84 days respectively. Mortality for patients with a Discriminant Function ³32
was greater in GM managed patients compared with GE at 28 (p=0.006), 56
(p=0.013), and 84 days (p=0.036).
Conclusion: Differences
exist between the management of jaundiced ALD between GM and GE. Such
differences may translate into improved outcomes.
Keywords: Alcoholic Liver
Disease; Jaundice; Alcoholic Hepatitis; Specialist Care; Corticosteroids;
Nutrition.
Introduction
The
development of jaundice in the context of active alcohol abuse often heralds a
grave prognosis. The pathogenic setting for this jaundice is likely to be either
acute alcoholic hepatitis (AAH) or advanced cirrhotic alcoholic liver disease (ALD).
In the case of AAH the short-term mortality may be as high as 60%1.
Overall five-year survival after the onset of jaundice amongst patients with
cirrhotic ALD is 33.3% and 57.5% for non-abstainers and abstainers respectively2.
The admission rate for ALD is known to be rising in Scotland3 and
alcohol related deaths doubled in Scotland between 1993 and 19994.
Patients
with jaundiced ALD are often admitted under the care of a General Physician.
Depending upon local practice such patients may remain in the care of General
Medicine (GM) or be transferred to the care of a Gastroenterologist (GE). A
recent paper based in the United States of America has indicated that a
Gastroenterology consultation significantly improves the outcomes of patients
presenting with decompensated cirrhosis5. The aim of the current
study was to determine whether GE management made a significant difference to
the outcome of patients with ALD presenting with jaundice.
Methods
The
clinical and laboratory records of patients with ALD identified by discharge
coding between June 1999 and December 2001 were reviewed. Only those patients
with a history of alcohol excess (estimated greater than 80g per day) for more
than five years until within three weeks of admission were included. A threshold
of a serum bilirubin greater than 80 mmol/l
on admission was used to identify those patients for study. This is because a
bilirubin concentration of 80 - 85mmol/l
has formerly been used to define patients with alcoholic hepatitis. Patients
whose in-patient stay or survival was less than 48 hours were excluded. Excluded
also were those patients presenting primarily with gastro-intestinal bleeding,
and those patients with or subsequently found to have viral hepatitis,
autoimmune liver disease or hepatocellular carcinoma.
Clinical
features (the presence of ascites and encephalopathy) were noted at the time of
admission. Laboratory results were recorded from within 36 hours of admission
and, in the case of GE managed patients, within 36 hours of the time of
assumption of care. Severe Alcoholic Hepatitis was defined using the modified
Maddrey’s Discriminant Function (mDF) 6,7:
mDF = [serum Bilirubin(mmol/l)
/ 17]
+
[prolongation of Prothrombin Time (seconds) x 4.6]
A
value of greater than or equal to 32 was used to define a group of patients with
severe alcoholic hepatitis at high risk of death.
Patients
admitted under the care of GM and who remained so for the duration of the
admission episode were regarded as being managed by GM. Patients whose
continuing care was assumed by GE were regarded as being managed by GE. A single
consultation without in-patient follow-up was not regarded as an assumption of
GE care. GE care was provided by a consultant general Gastroenterologist and a
consultant Gastroenterologist and Hepatologist, both supported by an Associate
Specialist and a Specialist Registrar.
The
in-patient management of these patients was recorded. In particular because of
their suggested role in the management of AAH, the use of corticosteroids and
nutritional support was noted. In addition as these patients are recognised to
be at increased risk of sepsis, the use of broad-spectrum antibiotics was noted.
Statistical
analysis was performed using SigmaStat v2.03,
SPSS Inc.
Results
Patient
Characteristics
In
total 97 admission episodes involving 86 individual patients were identified.
The mean age was 51.3 ±
1.0 years and 30% of the patients were female. GE managed the majority of
patients (62 patients). The median time to the assumption of care by GE was 2
days (range 0 –12).
There
were no significant differences between the GM and GE patients at the time of
admission, nor at the time of assumption of care by GE (Tables
1 and 2). The modified
Maddrey’s discriminant function at the time of admission was greater than or
equal to 32 in 72.5% and 65.7% of GE and GM patients respectively.
In-Patient
Management
In
all cases of GE management, GE care was for more than 50% of the admission
episode (median 85.7%). The median time to GE review was two days (range 0 –
12). The median hospital was 14 days (range 2 – 89), but this was
significantly greater for GE managed patients (17.5 [2 – 87] days vs
9 [2 –89]; p<0.001).
Significant
differences were apparent between GE and GM managed patients with respect to
corticosteroids, nutritional support and antibiotic prescription (Figure1).
Significantly more patients under GE care received presumptive antibiotic
treatment without specific laboratory or clinical evidence of sepsis.
In
total 53.6% of patients received nutritional support. Of these the majority
63.5% (33 patients) received dietetic advice and oral nutritional supplements.
The remainder attempted naso-gastric feeding, three of whom also received
peripheral intravenous feeding after failure to tolerate the enteral route.
Twenty-seven
patients had clinical or laboratory evidence of sepsis. Nine patients had
urinary tract infections, nine had pneumonia, five had cellulitis, and four had
evidence of spontaneous bacterial peritonitis.
Mortality
The
overall mortality was 27.8%, 34.0%, and 37.1% at 28, 56, and 84 days
respectively. The cause of death was noted to be hepatocellular failure in all
but one death that was attributed to the complications of a strangulated
umbilical hernia. Renal failure was an additional feature in 59% of deaths. On
admission 7 patients managed by GM had evidence of significant renal impairment
(serum creatinine > 150mmol/l).
Five GE managed patients had renal impairment at the point of assumption of care
(p=0.112). All of the GM managed patients with renal impairment died within 28
days. Two GE managed patients died in 28 days (p=0.045).
Sepsis
was felt to have contributed significantly in 26% of death at 28 days. Death was
associated with significant upper gastro-intestinal haemorrhage in only two
cases throughout the study period.
The
difference in all-cause and liver-related mortality between GE and GM managed
patients is shown in Table 3.
Amongst
patients whose mDF was greater than or equal to 32 on admission, the difference
in liver-related mortality persisted until 84 days (Figure
2).
Discussion
In
the United Kingdom ALD-related hospital admissions are increasing, as are
alcohol-related deaths. As a group whose response to treatment is often poor,
whose mortality is high, and whose compliance with subsequent treatment is in
doubt, decompensated ALD patients might not be perceived as attractive to
manage. However in the case of AAH, the patients are often young and their
pathology at least in part potentially reversible.
This
study has indicated that significant differences exist between specialist and
generalist management of jaundiced ALD. This was a retrospective study with all
the limitations associated with such. However a randomised study of generalist
versus specialist management would be ethically dubious. It was not possible to
identify how many of each group had alcoholic hepatitis, a combination of
alcoholic hepatitis and cirrhosis, or end-stage alcoholic cirrhosis. Hence the
use of the term ‘jaundiced alcoholic liver disease’. As coagulopathy amongst
other concerns often precludes liver biopsy in these patients, this report has
sought to study patients as they present to the physician clinically. Another
point of note is the trend towards greater renal impairment in the GM managed
patients. This might be thought to contribute to their worse prognosis. However
a significantly greater proportion of GE managed patients with renal impairment
survived beyond 28 days. Therefore despite the groups not being strictly
comparable, there were no significant differences between them on presentation.
The
differences in management may translate into improved outcome for these
patients. However as a group the difference in outcome was short-lived and any
benefit in specialist management limited to just 28 days. However when those
patients with a particularly poor prognosis (mDF ³32)
were analysed the benefit of specialist management was sustained to 84 days.
A
recent study has demonstrated improved outcome for patients with decompensated
cirrhosis when managed jointly by gastroenterologists and generalists as opposed
to generalists alone5. This was true for 30-day mortality and
readmission rate. Although this study had only 36% of patients with ALD and only
20% presenting with jaundice, the benefit of specialist intervention is
consistent with the current study.
The
benefits of corticosteroids and nutritional support in AAH remain controversial.
In the case of corticosteroids multiple randomised-controlled trials have been
performed, however their interpretation and application in clinical practice has
been hampered by widely varying inclusion and exclusion criteria6,7,8,9,10.
Meta-analyses have also delivered conflicting results11,12,13,14.
Whilst the picture is not clear, it is probable that the short-term mortality of
a select group of AAH patients with a high mDF is improved by steroids15.
Similarly
with nutritional support, trials have failed to inform clinical practice
clearly. There would appear to be improvement in patients’ nutritional status
and more rapid improvement in encephalopathy and other laboratory measures of
hepatic function, but no clear improvement in survival16,17. A recent
study has suggested that enteral nutrition may be as beneficial as
corticosteroid treatment18.
There
are no studies specifically investigating the role of antibiotic treatment in
AAH. However the early use of antibiotics seems logical as most studies report a
significant number of deaths from sepsis18,19. However the clinical
features of severe AAH with pyrexia and leucocytosis will often mimic infection.
A low threshold of suspicion for treatment of sepsis therefore seems
appropriate.
Thus
the treatment strategies assessed in this study are logical. However which, if
any, of these treatments improved the outcome of the jaundiced ALD patients
managed by GE cannot be determined. This study does suggest that a specialist
approach to these complicated patients had a beneficial effect. With the
potential advent of new therapeutic options for the treatment of this
devastating condition19, specialist involvement is imperative.
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