Why repeat liver function tests

Abnormal liver blood test results are relatively common and most people with these results have normal liver function. However, any abnormality does need to be investigated to find out what the cause is. Scans may be performed to help understand the cause of the abnormality and also to assess how significant any damage is. These may include imaging scans such as ultrasound, elastography scans such as FibroScan, CT or MRI scans , which help doctors get a better picture of the extent of any damage to the liver.

In certain cases a liver biopsy where a tiny piece of tissue is taken from the liver for examination may be considered to specifically diagnose a condition or provide information on the extent of scarring inside the liver.

If you are very unwell, you may be referred or admitted to hospital, although this is unusual — only a very small number of people with abnormal liver blood tests require admission.

Your doctor will explain your test results to you. If they are abnormal, your doctor will also explain the most likely cause, and how severely affected your liver may be. When a patient has been found to have an abnormal liver blood test, the next step is to establish the cause. This requires a second panel set of blood tests that look for potential causes such as viruses, problems with the immune system and rarer inherited conditions.

If you have NAFLD, the next step is to investigate the extent of the condition and if the liver is scarred or damaged. The level of scarring can be assessed using specialist scans or blood tests and your doctor can explain these to you.

If these tests are not able to assess any damage accurately, a liver biopsy may be considered to provide more detailed information. Because NAFLD is commonly associated with being overweight, there is evidence to suggest that losing weight through diet and exercise helps reduce the amount of fat in the liver and damage done to it.

The Government advises that both men and women should not regularly drink more than 14 units in a week. It is also important to have consecutive days off drinking a week to allow your liver to recover.

However, the National Institute for Clinical Excellence NICE guidelines recommend that if you drink alcohol in a harmful way, defined as more than 50 units of alcohol per week for men around 15 pints of beer and 35 units for women about 3. Not necessarily. If your results are abnormal your GP can advise you on the next steps to determine the cause and assess how serious the problem and any associated damage is. You need to see specialists at this point, which your doctor will arrange. The cohort was formed from patients with at least one abnormal analyte from a panel of eight - alanine aminotransferase ALT , aspartate aminotransferase AST , ALP, bilirubin, gamma-glutamyltransferase GGT , globulin derived , total protein, and albumin and no known liver disease.

Eligible patients from the participating GP practices were invited to attend special study clinics where the following information was obtained:. Patients were followed up for two years, at which point LFTs were repeated along with a further ultrasound of the upper abdomen results of the follow-on study will be reported at a later date.

A simple decision tree was constructed in Microsoft Excel Microsoft Corp. The strategies were developed in consultation with a GP and hepatologist P. Gill and J. Neuberger respectively who were aware of the relevant literature and guidelines. The root decision or starting point of the tree is the discovery of an abnormal LFT in primary care where the patient does not have known or self-evident liver disease.

From the root node we identified seven decisions that may be considered by a GP under such a scenario:. This could be considered the intuitive response by a GP on receiving an abnormal LFT in a patient without the indictors of a specific disease, and is the strategy recommended in the literature [ 1 — 5 ].

The rationale for this strategy is that ALT is the most specific indicator of viral hepatitis [ 4 ], and has been recommended as the testing criterion by other authors [ 16 — 18 ]. This is also the threshold for instigating viral therapy for HBV in certain treatment guidelines [ 20 — 22 ]. Screening has been shown to be cost-effective for people who were born in prevalent countries and it is likely that testing would be more cost-effective still in a population with abnormal LFTs [ 21 , 26 ].

There is also an option to take no action with respect to viral hepatitis, and while this may be a sound decision in some cases, for example when a LFT is ordered in the hope that a positive result will prompt a reduction in alcohol intake, this was not considered here. In this study the hepatitis status for all patients was known. Thus it was possible to evaluate the performance of each of the above strategies.

All 1, patients were used in the evaluation of strategy G, but for all other strategies the effective sample size was reduced because of missing data in some of the patient records.

Estimates of the proportion of patients undergoing viral tests, and the proportion of actual cases detected sensitivity were obtained using the sample of patients available for evaluating each strategy.

The positive predictive value of a strategy was defined as the proportion of hepatitis cases among those selected for viral testing. Confidence limits for this quantity were calculated using Wilson's method for Binomial data [ 27 ]. The direct costs incurred at the time of the test were the laboratory costs of the liver function and viral hepatitis tests personal correspondence with Pathology Lab Manager ; the GP costs for scheduling each test; and following up on results.

Administrative costs were estimated by estimating the time implications for a secretary to add patients to appointment slots and a receptionist to check the patient in for an appointment personal correspondence with MidReC: West Midlands Research Consortium. Figures correct as of February Non-health service costs patient travel cost and lost earnings were not measured, but are considered in the discussion.

The number of cases detected per patients was estimated as the sensitivity of the strategy cases detected divided by cases present multiplied by the prevalence per patients of viral hepatitis in the whole sample of 1, patients.

For each strategy the cost per case detected was then computed as the ratio of the cost per patient to the number of cases detected per patient.

The strategy which minimised this quantity was taken as the base case. For each alternative strategy the incremental cost-effectiveness ratio ICER was computed, defined as the incremental cost per additional case detected compared to the base case. The analysis is deterministic and does not consider the impact of sampling variability.

The results of these analyses were compared with published results of cost-effectiveness analysis of screening for chronic viral hepatitis, bearing in mind likely differences between a screening and a diagnostic population. We used this analysis to develop a "fast and frugal" heuristic [ 28 ] which we offer to readers for their consideration. One thousand, three hundred and forty-four patients consented to the study.

Fifty-four were excluded because they did not match the entry criteria in the protocol, along with a further 54 where data on at least one viral hepatitis test was missing Figure 1. This left 1, patients for this study. One hundred and five of these patients were from Lambeth and 1, were from Birmingham. The median interval between index and repeat testing was 31 days inter-quartile range days.

Thirteen of the 1, patients where the test result was available had chronic viral hepatitis - nine cases of hepatitis B and four cases of hepatitis C. This gives an estimate of 1. The demographic breakdown of patients with and without viral hepatitis is shown in Table 2.

The breakdown LFT results in the infected cases is given in Table 3. In 10 of these 13 cases, more than one analyte was abnormal. In eight cases the ALT was abnormal and was notably raised in six of those above twice the upper limit of normal. Eleven of the 13 patients with chronic viral hepatitis had an abnormality on the repeat LFT. There were two other cases where there were missing data among the repeat LFT panels. The country of origin was recorded in 1, of the 1, study cases, and of these, people were born in a country with an intermediate or high prevalence of viral hepatitis based on WHO definitions of prevalence [ 23 — 25 ] and 1, were from low-risk countries.

None of the 13 cases admitted to use of intravenous drugs at any time. As expected from the literature, ALT or AST levels when abnormal tended to be more extreme for cases with viral hepatitis than for cases that did not have this disease Table 4.

The sensitivity and positive predictive value of each detection strategy are given in Table 5. It can be seen that the recommended strategy A , of repeating the LFT and then doing a viral test if an abnormality persists, is highly sensitive. However, the predictive value is low 1. The more selective strategy of testing if the index ALT was over twice the upper limit of normal C has a higher predictive value, but is less sensitive.

The cost of the laboratory tests and the practice costs are given in Table 6. The average cost per case detected and the incremental costs of detecting each additional case are shown in Table 7. This strategy was therefore designated as the base case for the calculation of the ICERs. Strategy A, the intuitive and widely advocated practice of repeating LFTs, turns out to be the most expensive per case detected.

It is dominated by strategy G, where all patients have a viral test. Similarly strategy B viral test if the index ALT is abnormal is dominated by strategy D perform viral test if patient was born in an intermediate or high risk country. Strategy C viral test if the ALT is greater than two times the upper limit of normal can be eliminated by an extended dominance principle.

If strategy C is preferred to E, this can only be because the extra cases detected by C are deemed worth the extra cost. However, strategy D finds yet more cases than C at lower incremental cost.

Therefore either E or D are preferable to C. The cost-effectiveness of the remaining admissible strategies can be visualised from Figure 2. The dotted lines join strategies that cannot be eliminated by dominance principles. The absence of any explicit penalty for missing cases of viral hepatitis in this analysis implies that the costs of E, D and F are under-estimated with respect to G.

However, F must be regarded as highly competitive with G - it picks up almost as many cases and has very high efficiency in terms of cost per case detected. Cost per detected case for seven testing strategies. The number used differs slightly from the actual number of cases detected per patient in table 5 because of variation in the prevalence of the condition across the samples in which each strategy was tested.

The BALLETS study is the first GP based study where the entire cohort was comprehensively tested for additional diseases such as viral hepatitis after an abnormal LFT, using the full analyte panel and normal reference ranges. We have shown that an abnormal LFT alone does not select out a population where the prevalence rate approaches a threshold which would justify viral screening.

We have assessed the validity of the various strategies a GP could adopt, at least as far as viral hepatitis is concerned, when faced with an abnormal LFT of uncertain provenance. The intuitive response for a GP in such a situation would be to repeat the LFT, an approach advocated by current literature. This study shows that this may not be the optimal policy.

This strategy is the most expensive, even more so than viral testing all patients, as the costs incurred include repeating the LFT as well as viral testing the majority. The strategy of testing all people from prevalent countries is the second most efficient, in terms of cost per case detected, and detects almost twice as many cases as the most efficient strategy - testing for viral infection when two conditions birth in a prevalent country and an ALT greater than twice the upper limit of normal are satisfied.

The relative financial disadvantages of the strategy of repeating the LFT would be even greater if patient costs were included, as the extra visit would have to be factored in.

We conducted a literature review using the search strategy shown in Table 8 , with the aim of retrieving papers that studied a cohort of patients with abnormal LFT results to provide evidence on the probability of various liver diseases including chronic viral hepatitis given abnormal test results.

Any such studies would enable the precision of our observations to be strengthened. The search strategy returned 1, papers, including a previous review by Dufour et al. Only eight studies matched our requirement of following up patients with an abnormal LFT result.

Two additional articles were selected from the references of relevant studies. As a result, to the best of our knowledge, there are only ten studies where a cohort of asymptomatic patients with abnormal LFTs were followed up Table 9. However, one article was written in Korean only the abstract was translated , so was excluded from our analysis.

Two of the remaining nine English language papers described record linkage studies. One such study was based on the Korean insurance database that was linked with death certificates [ 30 ]. This study reported that increased ALT, even within the upper end of the normal range, was associated with eventual death from liver disease. A study carried out in Scotland linked general practice and hospital databases [ 31 , 32 ]. However, this was a retrospective study so a full liver screen was not conducted and follow-up was for a median of four years only, whereas many diseases, including chronic viral hepatitis, have much longer prodromal periods [ 33 ].

The other seven studies were prospective cohort studies, based on testing asymptomatic members of the general population. The famous Dionysos study based on three analytes from the LFT analyte panel [ 34 ] is included among these. In this study an impressive 6, citizens from two communities in northern Italy were screened.

The prevalence of viral hepatitis is much higher in this region because of a significant immigrant population, and they performed a more extensive analysis on the impact of viral hepatitis on LFTs. Of the Perhaps the most comprehensive prospective analysis looking at the effect of viral hepatitis on the individual analytes was carried out on a population of Japanese office workers [ 16 ].

The study used data from compulsory health checks, which included an ALT, AST and GGT panel along with certain additional tests, such as a viral screen, that were added for study purposes. The remaining four prospectively designed studies were carried out in general practices and were therefore closer in population terms to the BALLETS cohort. However, three of these were restricted to patients with persistently abnormal LFTs over a six month period [ 36 — 38 ] and one of these did not include a test for viral hepatitis.

The final prospective study by Whitehead was small and based on only one analyte [ 39 ]. After this review of the literature we concluded that there has been no published study that fully investigated a cohort of patients in primary care with an abnormal LFT result from the full LFT analyte panel. The main strength lies in the unique nature of the BALLETS cohort, being the only prospective study that has looked at the consequences of an abnormal LFT from a full analyte panel in primary care.

The various component of the liver function indicates the type of liver cells and the disease which might be causing the liver test abnormality. The liver function test consists of:. Specialists will also look at another panel of the blood test to assess the actual function synthetic function of the liver.

This panel will include:. The normal range of blood tests is usually dependent on the laboratory that has conducted the tests. The normal range will most often be given along with the result of the test. If it is not given along with the results, it is important to find out about the normal range from the medical specialists as it might have implication in the assessment and management of the liver function test. It is important to highlight here that about 5 per cent of patients with advanced liver disease cirrhosis will have normal liver function test.

Therefore, the results of the blood test will have to be interpreted according to the clinical context in which the request was made. Most people find out about abnormal liver function when they have a set of blood tests, which include liver function test for an unrelated reason or for routine health checks.

It is very important to understand that liver disease is completely asymptomatic in the majority of cases until it is in a very advanced stage. When a blood test reveals that there is evidence of abnormal liver function, a review from a healthcare specialist is essential.

Most of the time, the tests have to be repeated again to confirm the abnormal results and also to assess the trend of liver dysfunction. This will help the health care professional to decide on the seriousness of the condition and refer the patient to the appropriate liver specialist either as an outpatient clinic review or, rarely, directly admitted to hospital for further assessment and treatment.

There are various reasons why liver tests may be abnormal. The most common reasons why liver tests are found to be abnormal in the UK are because of fatty liver, excess alcohol consumption or presence of viral hepatitis like Hepatitis B or C. Other common causes of abnormal liver tests include medications and herbal supplements. There are many rarer causes of liver test abnormalities, which will be investigated by the liver specialists by doing specific blood tests.

When an abnormal blood test is found, the GP will assess the common causes of liver disease. Most commonly, the GP will refer the patient to a liver specialist, also known as a hepatologist , for further advice and guidance on future management. The hepatologist will take a detailed history, including the amount of alcohol consumption, assess metabolic factors, including diabetes and hypertension, and assess the risk for chronic viral hepatitis including Hepatitis B or C. The specialist will do an extended set of bloods to assess for rarer causes of liver disease.

An ultrasound scan of the liver will also be requested routinely to assess for any focal abnormality of the liver. Fibroscan is another specialist scan that will be requested by the hepatologist to determine whether there is a presence of any evidence fibrosis or cirrhosis advanced liver disease.

The hepatologist will advise on the management of the liver condition, which could include lifestyle changes or medicines to treat specific liver conditions.