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PRIMARY CARE: Paul Sherwood, Iain Lyburn, Sandy Brown, and Stephen Ryder How are abnormal results for liver function tests dealt with in primary care? Audit of yield and impact BMJ 2001; 322: 276-278 [Abstract] [Full text]

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Iatrogenic Effects?

Cory Mermer   (3 February 2001)

Liver Biopsy for alcoholics

Tim Harding   (6 February 2001)

An ivory tower view

G Wheatley   (6 February 2001)

Lack of Ethical Approval is a Disgrace

Gregor Venters   (23 February 2001)

Abnormal LFT are often under investigated in secondary care too!

Julia Newton   (23 February 2001)

Costs of Investigating Abnormal Liver Biochemistry in Asymptomatic Individuals

Ian Cadden   (8 June 2001)

Iatrogenic Effects? 3 February 2001
Cory Mermer, Medical Researcher/Writer Optimal Wellness Center (www.mercola.com) Send response to journal: Re: Iatrogenic Effects?	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.
Liver Biopsy for alcoholics 6 February 2001
Tim Harding, Consultant Gastroenterologist Lagan Valley Hospital Send response to journal: Re: Liver Biopsy for alcoholics	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.
An ivory tower view 6 February 2001
G Wheatley, General Practitioner Surrey Send response to journal: Re: An ivory tower view	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.
Lack of Ethical Approval is a Disgrace 23 February 2001
Gregor Venters, GP Principal Pentlands Medical Centre, Currie, EH14 5QB Send response to journal: Re: Lack of Ethical Approval is a Disgrace	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
Abnormal LFT are often under investigated in secondary care too! 23 February 2001
Julia Newton, Senior Lecturer in Geriatric Medicine University of Newcastle upon Tyne Send response to journal: Re: Abnormal LFT are often under investigated in secondary care too!	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.
Costs of Investigating Abnormal Liver Biochemistry in Asymptomatic Individuals 8 June 2001
Ian Cadden, Registrar in Medicine Royal Victoria Hospital, Belfast Send response to journal: Re: 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.