Any elevated liver function

For the rest of the analyses imputation according to the median reference ranges is used.

Of 15 308 participants in the universal arm of the trial, 13 276 (86.7%) had at least one valid measurement of liver function. Participants who did not have a valid test result were more likely to be female (OR 1.33 [1.19, 1.49]), were slightly older (median age 81.5 years for those without a valid test result compared with 80.2 years for those with a test) and had more missing data with respect to comorbidity compared with those people who had at least one valid test result.

Overall, 16.1% of those with one or more valid measurement had at least one elevated liver function test. The most common elevated liver function test within this population was ALP with 9.2% (95%CI [8.7%, 9.7%]) of people having a result above the ULN (see Table 7-8). Only 5.4% (95%CI [5.0%, 5.8%]) of people had an elevated bilirubin test, whilst an even smaller proportion had an elevated AST result, 3.3% (95%CI [3.0%, 3.7%]) of those with a valid measurement. The majority of subjects with an elevated

measurement had a test result less than or equal to 2x the ULN: 86.2% AST; 90.0% ALP, 93.8% bilirubin.

Table 7-8 Prevalence of elevated liver function tests Elevated test(s)

(Number with valid test)

Number elevated (% of elevated) % of valid tests elevated [95% CI] Any elevated (N=13546) 2175 16.1 [15.4, 16.7] AST (N=12826) 429 (100) 3.34 [3.04, 3.67] ≤ 2x ULN 370 (86.2) 2.88 [2.60, 3.19] Above 2x ULN 59 (13.8) 0.46 [0.35, 0.59] ALP (N=13499) 1246 (100) 9.23 [8.75, 9.73] ≤ 2x ULN 1122 (90.0) 8.31 [7.85, 8.79] Above 2x ULN 124 (10.0) 0.92 [0.76, 1.09] Bilirubin (N=12690) 690 (100) 5.44 [5.05, 5.85] ≤ 2x ULN 647 (93.8) 5.10 [4.72, 5.50] Above 2x ULN 43 (6.2) 0.34 [0.25, 0.46]

AST and ALP (N=12794) 90 0.70 [0.57, 0.86]

AST and bilirubin (N=12021) 42 0.35 [0.25, 0.47] ALP and bilirubin (N=12648) 67 0.52 [0.41, 0.67] AST, ALP and bilirubin

(N=11994)

9 0.07 [0.03, 0.14]

All 3 within reference range (N=11994)

7.4 Discussion

7.4.1 Key findings

I found that nearly 1 in 6 of the general population aged 75 and over had at least one elevated liver function test. Over half of these abnormalities can be accounted for by an elevated measurement of ALP (9.2% of all subjects) and the vast majority were within 1x the upper limit of normal for the test

measured. Very few participants had more than one recorded elevated liver function test (<1% for any combinations of one or more elevated liver function tests) with only 9 participants having all 3 liver function tests recorded as elevated.

7.4.2 Strengths and limitations

In this study I was able to assess, for the first time, the liver function of a representative randomly selected community-based sample of people aged 75 and over. That blood samples were available for most of the people in the MRC elderly gives this study a distinct advantage over many other studies looking at liver function insofar as the study population was not selected on the basis of known or suspected liver disease.

Arguably, abnormalities of AST, ALP and bilirubin are of secondary

importance when looking at liver function compared with a measurement of alanine aminotransferase (ALT) which is specific to the liver. I was unable to investigate this as a blood test for this enzyme was not a part of the original study design.

As a result of the multi-site nature of this large study I was reliant on data collection from several laboratories across the UK. Not all laboratories were able to provide reference ranges for the liver function tests so I relied on imputation for nearly half of the reference ranges. Basing the upper limit of normal on the median reference range for those practices where imputation was necessary may under- or over-estimate the true level of elevated liver function in this population. This could make a significant difference to the proportion of older people who would be considered to have elevated liver function as seen particularly in the measurement of ALP. Using the minimum reference ranges for elevated upper limits an estimated 41.3% of participants had an elevated ALP test result compared with only 9.2% when using the median reference range.

Data having been collected from multiple laboratories also meant that I was unable to describe absolute values of enzymatic activity as there was not one uniform test in operation at all of the different sites.

In some laboratories there were different normal reference ranges provided for ALP for people aged 60 and above, those aged less than 60 and in some cases for children. It may be that reference ranges for the LFTs measured should be provided in even finer categories than this. I examine the

association between abnormal measurements and age in the next chapter.

7.4.3 Comparison with previously published work

Information on the prevalence of elevated liver function in the UK is surprisingly lacking. These results show a lower prevalence of elevated

reported in a recent study of adults of all ages from Scotland.66 This is perhaps expected as the population within this study was selected on the basis that subjects already had a measurement of liver function contained within their primary care records. The authors acknowledge that they do not know why liver function tests were requested and this is likely to include the investigation of suspected liver disease leading to a non-representative sample of the general population.

In a study in America,76 again only a selected group of participants had a blood test, and it is likely that the true population prevalence of elevated liver function tests may have been over estimated. Indeed, 12.8% of those with a measurement of AST had an elevated test, nearly four times that seen in my study. Another study from the USA also showed a slightly higher prevalence of elevated AST to that which I have described in this study, with 3.7% and 4.9% of the population aged 20 or over having an elevated AST in 1988-1994 and 1999-2002 respectively.71 However, given that my study looks only at people aged 75 and over, it may be that the prevalence of elevated liver function tests in a population of older people is indeed lower than that found in the general adult population of all ages. This is supported by data from America where the prevalence of elevated ALT or AST in the population aged 70 or older was reported as 4.9%, statistically significantly lower than the prevalence of elevated transaminases in younger age groups.70

7.4.4 Conclusions

Current guidelines recommend that liver function tests should be carried out before and within 1-3 months of starting treatment on statins to monitor for signs of altered liver function.111 With an estimated 40% of all 75-79 year olds have at least one prescription for statins annually,112 incidental findings of

elevated LFTs in this age group of the population in the absence of symptoms are likely to occur regularly. The study reported in this chapter has shown that abnormalities in liver function are fairly common in people aged 75 and over. Using population estimates for 2008 if every person aged 75 and over was to undergo these three blood tests elevated levels in one or more of the LFTs would be found in 770,000 patients. It will be important to determine the correct course of action for the follow-up and assessment of older people with elevated liver function tests to avoid unnecessary follow-up and investigation and potential anxiety for an individual.