How are abnormal results for liver function tests dealt with in primary care? Audit of yield and impact
BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7281.276 (Published 03 February 2001) Cite this as: BMJ 2001;322:276
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I was surprised to read in Sherwood et al,the fact that if a patient
was elderly this was regarded as an acceptable reason for not
investigating abnormal LFT. Abnormal LFT predict pathology with the same
degree of certainty as in younger age groups and being old should not be a
contraindication to adequate and appropriate investigation and follow up.
We have completed a similar audit to that of Sherwood et al in a
cohort of over 70 year old inpatients admitted to a district general
hospital with an age related admission policy.
Our findings were similar. Of 502 unselected over 70 year old
inpatients included, 15% did not have LFT tested while an inpatient, LFT
were normal in 157(31%). 8% had abnormalities suggestive of myocardial
damage and were subsequently excluded from further study.
The remaining 229(46%) had an abnormality of at least one or more
liver function test. In this group, no liver biopsies were performed, 56
abdominal ultrasounds, 2 ERCP, viral hepatitis markers in 5%, autoantibody
screen in 9%. A cause for the abnormality was documented in only 14
individuals.
The cohort were followed up for 3 years. 60% died during that
period, of the 91 alive at 3 years 18(20%) had never had their LFT
rechecked by either the hospital or the GP, 22(24%) still had abnormal LFT
and 51(56%) had returned to normal.
In addition, to illustrate that abnormal LFT are not a benign finding
we examined cumulative survival (Kaplan-Meier). Over 70 year old
inpatients with the severest abnormalities of LFT (i.e. transaminase
>3x upper limit of normal, abnormalities of all 5 LFT, alkaline
phosphatase > 2x upper limit of normal) had a significantly poorer
cumulative survival at 3 years compared to the group with normal LFT
(p<0.0001).
Abnormal LFT must be recognised, and investigated in all groups
irrespective of age. If reversible causes of liver disease are not to be
missed, it is essential that abnormalities of liver function are followed
up with appropriate action and shown to return to normal.
Competing interests: No competing interests
Sir
The paper "How are abnormal results for liver function tests dealt
with in primary care? Audit of yield and impact"
(Paul Sherwood, Iain Lyburn, Sandy Brown, and Stephen Ryder
BMJ 2001; 322: 276-278) states that ethical approval was not sought for
the study. This was because "further investigation ..... was thought to
be clinically indicated".
No evidence was given for why this was case. I have been unable to
find any recommendations for investigation of abnormal liver function
tests (LFTs) found in general practice. Most of the studies cited were
based in hepatology clinics and findings cannot be applied to primary care
patients.
However 101 patients had a potentially dangerous procedure, namely a
liver biopsy, performed to which they would not otherwise have been
subjected.
That a group of doctors should think such a study did not require
ethical approval is worrying. That the BMJ should print original research
without prior ethical approval is a digrace.
Yours sincerely
Gregor Venters
Competing interests: No competing interests
I was surprised by Sherwood et al's conclusion that
"abnormal results are often not investigated". Closer
inspection shows this to be a rather distorted
impression.
Of the 873 patients with abnormal LFTs & adequate
follow-up data, 157 were deemed to need further
investigation, and of these, 91 (10%) remained
uninvestigated. If the authors describe a proportion of
10% to be "often", it rather begs the question of what
terms they would use to describe more frequent events.
The criteria for further investigation were not stated.
Were these criteria from accepted, credible national
guidelines, or were they at the discretion of the study
hepatologist? Of the 101 liver biopses peformed, the
authors give arguements for advantage to the patients
concerned in only six (the four patients with
haemochromatosis & the two with autoimmune
hepatitis). For the others, making such an early
diagnosis could easily be a disservice, by simply
bringing forward bad news with no realistic hope of
improving their overall prognosis. Against this
background, it is surprising that only 18 patients (all
with LFTs reverted to normal) declined a liver biopsy out
of 119 patients who were offered it.
In their introduction the authors make the unsupported
and rather unlikely-sounding assertion that "there is a
widespread assumption by both patients & doctors that
all abnormal liver biochemistry is due to alcohol
excess". Still, one might stick one's neck out &
hypothesize that patients & GPs think the majority of
abnormal liver biochemistry is due to alcohol excess.
This study actually supports such a hypothesis. While
by no means all abnormalities on biopsy were due to
alcohol excess, some 68/101 were. The authors fail to
state what benefits such early disgnosis brings, except
to speculate that this "may impact on behaviour",
though they present no evidence in support of such a
use of liver biopsy.
The authors finish by saying they intend to "complete
the audit cycle" & "reaudit" this work. They appear
confused as to whether their work is research or audit. I
could help them out by describing their work as a
cohort study, examining the effect of more intensive
investigation of patients with abnormal LFTs and
contrasting this to usual care. Audit, on the other hand,
requires criteria & standards to be set before
investigation, a feature not obvious from this work.
Considering this, I was extremely surprised to read that
this cohort study, involving invasive investigation
(including 101 liver biopsies), was not presented to an
ethics committe for prior approval. Liver biopsy carries
an appreciable risk, both of morbidity and mortality. The
onus is on the researchers to show that the potential
gains to the patients involved are worth this risk, and
that patients were given clear information to allow them
to make their own decisions about participating.
Finally, it is unfortunate (but not unusual) that the one
paper in the primary care section of the BMJ this week
should be without any general practice input, either in
the study team or in its perspective. There is useful
work to be done in this area, about the decision-making
by patients and GPs on the further investigation of
abnormal LFTs, but it is unlikely to be usefully informed
by an imposed and arbitrary set of standards and
"guidelines" from a rather ivory tower hospital view. It
illustrates how much needs to be done to encourage
and fund more meaningful work from within general
practice itself.
Competing interests: No competing interests
The Paper by Sherwood et al raise important points. In it they appear
to advocate liver biopsy for patients with abnormal LFTs, negative
serology and a strong alcohol history. Can the authors support their
(unreferenced) statement that results from such biopsies actually
influence subsequent drinking behaviour? If not, putting someone through a
procedure with potential serious morbidity or mortality may be hard to
justify.
No comment on complications is made in this paper - this perhaps is
of particular concern in view of the fact that ethical approval was not
sought.
Competing interests: No competing interests
Sherwood et al note that "Liver enzyme concentrations that are
chronically increased can result from chronic high alcohol consumption,
obesity (particularly in men), and smoking (in women)."
However, this statement ignores the fact that many pharmaceuticals
can elevate liver enzymes as well. This may have some bearing on the fact
that some primary care physicians are not adequately following up on
abnormal liver function tests.
For example, if they are seeing greater numbers of patients with
elevated liver enzymes, due to increasing prescription rates of drugs that
adversely affect the liver (e.g., Statins), they may begin to pay less
attention to the abnormal results. In other words, the “abnormal” results
may seem more normal.
Another, somewhat less innocuous possibility is that some physicians,
believing that these abnormal test results are drug-induced, are more
prone to ignore them in order to not call attention to these adverse
effects.
One recent study notes that “Monitoring of liver function varied
widely” for patients taking statin drugs (1). Therefore, not only may
abnormal liver function tests not be followed up correctly, but they also
may not be done where appropriate in the first place.
Reference:
1. Abookire SA, Karson AS, Fiskio J, Bates DW. Use and monitoring of
"Statin" lipid-lowering drugs compared with guidelines. Arch Intern Med
2001 Jan 8;161:53-8.
Competing interests: No competing interests
Costs of Investigating Abnormal Liver Biochemistry in Asymptomatic Individuals
The advent of automated laboratory testing has led to multiple
investigations being used to investigate those with non-specific symptoms.
This will invariably produce asymptomatic individuals with abnormal tests.
Sherwood et al highlight the importance of correctly evaluating such
individuals with deranged liver function tests at a primary care level
(1).
Recent reports suggest that as many as 6% of asymptomatic patients will
have an abnormality of liver function tests picked up on “screening” (2).
Sherwood et al demonstrated that 11% of patients in their study had
undetected major liver disease which would have benefited from hospital
follow-up.
An audit carried in our unit supports this observation that a significant
percentage of asymptomatic individuals with abnormal liver biochemistry,
have underlying liver disease. During the period from July 1999 to March
2000, all patients referred to the liver unit of the Royal Victoria
Hospital, Belfast, with abnormal LFTs detected on “screening”, were
followed to diagnosis. Each patient underwent various biochemical,
immunological, virological and radiological tests deemed necessary to
establish a diagnosis. In 38% of these individuals a diagnosis was
established for which a specific treatment was indicated. Diagnosis made
included primary biliary cirrhosis, hepatitis C, drug-induced hepatitis,
hepatic steatosis and alcoholic liver disease. As in previous studies,
hepatic steatosis was the most prevalent diagnosis (3).
In the current economic climate, cost-effectiveness of any policy is
obviously of paramount importance. We calculated the total costs
encountered in the investigation of these patients including the cost of
new patient referral and review clinic appointments, together with
investigation costs. We have established that an approximate cost of 270
is incurred to provide a diagnosis.
To conclude, we agree with Sherwood et al – these patients with
persistently abnormal test results benefit from referral to a
Hepatologist. The costs of identifying diagnoses in these individuals are
small and should not discourage those in primary care from making the
initial referral.
References :
1 Sherwood P., Lyburn I., Brown S., Ryder S. How are abnormal
results for liver function tests dealt with in primary care? Audit of
yield and impact. British Medical Journal 2001; 322: 276-278.
2 Gopal DV., Rosen HR. Abnormal findings on liver function tests.
Postgraduate Medicine 2000; 107(2): 100-114.
3 Daniel S., Ben-Menachem T., Vasudevan G., Ma CK., Blumenkehl M.
Prospective evaluation of unexplained chronic liver transaminase
abnormalities in asymptomatic and symptomatic patients. American Journal
of Gastroenterology 1999; 94(10): 3010-3014.
Competing interests: No competing interests