Discussion

3.4.1 Key findings

This study has described a 45% increase in the incidence of cirrhosis in the UK in the decade between 1992 and 2001 and a 68% rise in the prevalence. Cirrhosis occurred more commonly and at younger ages in men than women. Nonetheless, a significant increase in incidence was seen for all age groups and for both sexes across the period under study. Incidence of both alcoholic and non-alcohol-related cirrhosis increased in males and in females during the period.

Applying the 2001 prevalence and incidence figures to the 2008 age- and sex- stratified population of the UK, I estimate that, over the age of 25, at least 31,000 people in the UK are currently living with cirrhosis and approximately 7100 people are being newly diagnosed with this disease each year. If I use the estimate from the wider definition of cirrhosis this figure increases to an estimated 8000 people being newly diagnosed with cirrhosis each year. These figures are still likely to be an underestimate of the burden of cirrhosis since they are based on diagnosed disease and do not take into account the possibility of a continuing increasing trend. This clearly represents a

challenge for health care services and will have substantial implications for the future trends in mortality from this disease.

3.4.2 Strengths and limitations

This is the first UK-wide population-based study of the occurrence of cirrhosis. I have examined contemporary data from general practices representative of the UK collected over a period of 10 years. The collection of data within the

the same ascertainment biases as may be present in smaller, hospital-based series.

The biggest potential limitation of this study lies with the case definition, having included as cases all patients with any mention of cirrhosis,

oesophageal varices or portal hypertension within the primary care records. Although it is possible that portal hypertension and oesophageal varices are manifestations of diseases other than cirrhosis it was decided to include these codes within the list for cirrhosis as these symptom are widely regarded as being representative of cirrhosis in developed countries. The validation exercise, which took the form of a case note review, showed that the majority (75%) of the sampled cases had an assertion of cirrhosis within the medical records. Of the remaining 25% of patients, 8/9 had a confirmed chronic liver disease with the potential to develop cirrhosis, although cirrhosis itself was not recorded in the notes available to us. All of the confirmed diagnoses

examined in the case note review had been communicated to the GP directly from secondary care. It is reasonable to suppose that this is a sufficiently robust definition to accurately capture cases of cirrhosis recorded in the GPRD and in such a way which is easily replicated allowing valid examination of trends over time. Although I may have inadvertently included as cases a few patients who did not have cirrhosis it is more likely that I am missing cases of cirrhosis where diagnosis was unconfirmed and/or not fed back from

secondary care into the primary care records. This finding of an increase in incidence is unlikely to be due to increased ascertainment through diagnostic procedures as UK Hospital Episode Statistics report a decrease in the number of diagnostic fibre optic examinations of the upper gastrointestinal tract (-4%) in the period 1995/6 to 2004/5.83

While it was not possible to assign a presumed aetiology to 39% of cases from the available data this is similar to the largest previous study of cirrhosis with 35% being labelled as cryptogenic cirrhosis.37 I have considered all patients with specific recording of alcoholism as having alcoholic cirrhosis. Owing to the known limitations of recording and referral for alcohol-related problems by GPs within this dataset,84 it is likely that I have underestimated the number of patients with alcoholic cirrhosis. Although it is possible in a patient with recorded alcohol problems that alcohol intake itself was not the underlying cause of the cirrhosis, it is more likely that the true proportion of alcoholic cirrhosis is greater than the 50% seen in these data.

3.4.3 Comparison with previously published work

The largest study, prior to this study, looking at the incidence of cirrhosis in the UK was a summary of data collected over 18 years in the 1960s and 1970s.37 This previous study, which comprised 512 people identified to have cirrhosis, reported an incidence of cirrhosis of 10.3 per 100,000 population aged 15 years and over from patients diagnosed in a single district general hospital in west Birmingham and from Coroner‟s post-mortem reports. Though

representative of the population served by this hospital, these figures are not generalisable to the rest of the UK as the West Midlands region has a higher than average mortality from liver disease compared with the general

population of the UK.39 With any hospital-based series there is the potential for an ascertainment bias with active case finding being employed, leading to a further over-estimate of incidence. In addition, in the study by Saunders et al, 11.3% of the subjects included as incident cases were as a result of

The results displayed in this study show a higher or similar incidence of cirrhosis compared with the previous studies of cirrhosis in the UK37 38 40 but owing to the small, non-representative nature of these studies, and a lack of clarity as to exact methods used, direct comparisons should be avoided. This study is the only study based on a contemporary, representative sample of the entire UK population and has utilised data collected for general medical

purposes over a period of 10 years.

My data contrast with recent data from a hospital-based study in Denmark where no discernible trend in incidence of alcoholic cirrhosis was seen from 1994-2005.45 The figures reported in this study similarly showed a higher incidence and prevalence of cirrhosis for men than women, and for those aged between 45 and 64 years of age, although the crude incidence figures for alcoholic cirrhosis were higher than I saw in my study. Other data from Scandinavia report similar figures to those reported in this chapter for Gothenburg, Sweden (incidence of 15.3 per 100,000 person years)85 and Oslo, Norway (incidence of 13.3 per 100,000 person years)86 but a much lower incidence for Iceland (incidence of 3.3 per 100,000 person years).85

I have presented the first data quantifying the current burden of alcoholic cirrhosis in the UK but it is important to note that the incidence of non-alcohol related cirrhosis also increased over this period. Though it is possible that some of these cases were indeed misclassified alcoholic cirrhosis, it is also possible that other causes of cirrhosis are also on the increase. From a public health perspective a particularly important and potentially modifiable set of risk factors are those of obesity and its relationship with type 2 diabetes. Where fatty liver leads to steatohepatitis, fibrosis can occur in roughly one third of

in 73% of patients with „cryptogenic‟ cirrhosis.87 Although cirrhosis is far from recognised as an end-point for diabetes or obesity the sustained increase in these two potential risk factors may lead to further increases in the incidence of cirrhosis in the UK in the years to come.

3.4.4 Conclusions

Liver disease is one of very few chronic diseases where mortality in the UK has increased over the past three decades.88 In contrast, mortality from ischaemic heart disease, cerebrovascular diseases and respiratory diseases have all decreased. With a minimum estimate of 31,000 people over the age of 25 living with cirrhosis, a figure which is likely to increase, and with no good treatment options other than liver transplant, mortality from this disease will continue to rise.

Although the accuracy of defining true incidence is somewhat difficult with a chronic condition with heterogeneic presentation such as cirrhosis the figures reported in this study represent the most up-to-date estimates of the absolute rates and trends in incidence and prevalence of cirrhosis in the UK having used population-based data over a period of 10 years.

Cirrhosis represents a serious and growing burden of morbidity in the general population of the UK. The continued rise in cirrhosis has significant